Novel compounds and compositions for the inhibition of nampt

ABSTRACT

The present invention relates to compounds and compositions for the inhibition of NAMPT, their synthesis, applications and antidotes. An illustrative compound of the invention is shown below:

PRIORITY CLAIM

This application claims priority from U.S. provisional applications Ser.Nos. 61/379,789 and 61/379,796 filed Sep. 3, 2010, U.S. provisionalapplications Ser. Nos. 61/386,023 and 61/386,028 filed Sep. 24, 2010,U.S. provisional applicaton Ser. No. 61/475,813 filed on Apr. 15, 2011,and U.S. provisional application Ser. No. 61/483,242 filed on May 6,2011, the contents of which are fully incorporated herein by referencein their entirety.

FIELD OF THE INVENTION

The present invention relates to compounds and composition forinhibition of Nicotinamide phosphoribosyltransferase (“NAMPT”), theirsynthesis, applications and antidote.

BACKGROUND OF THE INVENTION

Nicotinamide adenine dinucleotide (NAD) plays fundamental roles in bothcellular energy metabolism and cellular signaling. In energy metabolism,the chemistry of the pyridine ring allows NAD to readily accept anddonate electrons in hydride transfer reactions catalyzed by numerousdehydrogenases.

The preparation of a class of compounds, comprising several subclasses,which act as inhibitors of the formation of nicotinamide adenylnucleotide, and their use thereof as anti-tumour agents, is alreadydescribed in the patent applications WO00/50399, WO97/48695, WO97/48696,WO97/48397, WO99/31063, WO99/31060, WO99/31087, WO99/31064, WO00/50399,and WO03/80054.

One of these inhibitors,(E)-N-[4-(1-benzoylpiperidin-4-yl)butyl]-3-(pyridine-3-yl)-acrylamidealso known as APO866, FK866, WK175, or WK22.175 and hereinafter referredto as FK866 [International Non-proprietary Name], is especiallydescribed in the literature as an anticancer agent. FK866 may be usedfor treatment of diseases implicating deregulated apoptosis such ascancer. It has been demonstrated in the prior art that FK866 interfereswith nicotinamide adenine dinucleotide (also known and hereinafterreferred to as NAD) biosynthesis and induces apoptotic cell deathwithout any DNA damaging effects.

Additionally, FK866 ((E)-N-[4-(1-benzoylpiperidin-4-yl) butyl]-3-(pyridin-3-yl) acrylamide) induces apoptosis in HepG2 cells withouthaving primary effects on cellular energy metabolism. (Hasmann M,Schemainda I. FK866, a Highly Specific Noncompetitive Inhibitor ofNicotinamide Phosphoribosyltransferase, Represents a Novel Mechanism forInduction of Tumor Cell Apoptosis. Cancer Res 2003; 63:7436-7442.[PubMed: 14612543]) Instead of causing immediate cytotoxicity, itinhibits NAMPT and depletes the cells of NAD, suggesting that FK866could be a promising agent against cancer cells that rely onnicotinamide to synthesize NAD. The crystal structure of the NAMPT-FK866complex reveals that the compound binds at the nicotinamide-binding siteof NAMPT to inhibit its activity. FK866 has been tested in a murinerenal cell carcinoma model and shown to display anti-tumor,antimetastatic, and anti-angiogenic activities (Drevs J, et al.Antiangiogenic potency of FK866/K22.175, a new inhibitor ofintracellular NAD biosynthesis, in murine renal cell carcinoma.Anticancer Res 2003; 23:4853-4858. [PubMed:14981935]).

In a mouse mammary carcinoma model, FK866 also induces a delay in tumorgrowth and an enhancement in tumor radiosensitivity accompanied withdose-dependent decreases in NAD levels, pH, and energy status. Achemosensitizing effect of FK866 has also been observed onanti-neoplastic 1-methyl-3-nitro-1-nitrosoguanidinium (MNNG)-inducedcell death in THP-1 and K562 leukemia cell lines (Pogrebniak A, et al.Chemopotentiating effects of a novel NAD biosynthesis inhibitor, FK866,in combination with antineoplastic agents. Eur J Med Res 2006;11:313-321. [PubMed: 17052966]).

The efficacy of GMX1777 was evaluated in xenograft models and thepharmacokinetic profile of GMX1778 and its effect on nicotinamideadenine dinucleotide cellular levels was measured by liquidchromatography/mass spectrometry. (Beauparlant P., et al. Preclinicaldevelopment of the nicotinamide phosphoribosyl transferase inhibitorprodrug GMX1777. Anticancer Drugs. 2009 June; 20(5):346-54).

GMX1777 is a water-soluble intravenously administered prodrug of GMX1778that Gemin X in-licensed from LEO Pharma (LEO numbers: EB1627 andCHS828, respectively). These compounds and other substitutedcyanoguanidines have the structures of Table 1. None of the compounds ofthe present invention are cyanoguanidines.

TABLE 1

A

B1

B2

CSubstituted Cyanoguanidines with Defined Pharmacological Effects:

-   A Cytotoxic CHS 828;-   B Potassium channel openers pinacidil (B1) and 12 g of compound as    described in Perez-Medrano et al (B2); and-   C Histamine-II receptor antagonist cimetidine. (from Lövborg et al.    BMC Research Notes 2009 2:114 doi:10.1186/1756-0500-2-114)

More recently, CHS-828 has been identified as a NAMPT inhibitor (OlesenU H, et al. Anticancer agent CHS-828 inhibits cellular synthesis of NAD.Biochem Biophys Res Commun 2008; 367:799-804. [PubMed: 18201551]).CHS-828 has been shown to potently inhibit cell growth in a broad rangeof tumor cell lines, although the detailed mechanism for this inhibitoryeffect of CHS-828 remains undetermined (Ravaud A, et al. Phase I studyand guanidine kinetics of CHS-828, a guanidine-containing compound,administered orally as a single dose every 3 weeks in solid tumors: anECSG/EORTC study. Eur J Cancer 2005; 41:702-707. [PubMed: 15763645]).Both FK866 and CHS-828 are currently in clinical trials for cancertreatments.

There are numerous uses for drugs which inhibit NAMPT.

Lack of NAMPT expression strongly affects development of both T and Blymphocytes. By using mutant forms of this protein and awell-characterized pharmacological inhibitor (FK866), authorsdemonstrated that the ability of the NAMPT to regulate cell viabilityduring genotoxic stress requires its enzymatic activity. Collectively,these data demonstrate that NAMPT participates in cellular resistance togenotoxic/oxidative stress, and it may confer to cells of the immunesystem the ability to survive during stressful situations such asinflammation. (Rongvaux, A., et al. The Journal of Immunology, 2008,181: 4685-4695).

NAMPT may also have effects on endothelium (EC) in relation to highglucose levels, oxidative stress and on aging. It is also believed thatNAMPT may enable proliferating human EC to resist the oxidative stressof aging and of high glucose, and to productively use excess glucose tosupport replicative longevity and angiogenic activity.

SUMMARY OF THE INVENTION

One aspect of this invention is the provision of compounds,compositions, kits, and antidotes for the NAMPT pathway in mammalshaving a compound of the Formula I:

wherein:

-   R is an aryl, heteroaryl, C₃-C₈ cycloalkyl, C₃-C₈ cycloalkenyl,    heterocycloalkyl, arylalkyl-, (heteroaryl)alkyl-, (C₃-C₈    cycloalkyl)alkyl-, (C₃-C₈ cycloalkenyl)alkyl-,    (heterocycloalkyl)alkyl-, (aryloxy)alkyl-, (heteroaryloxy)alkyl-,    (C₃-C₈ cycloalkyloxy)alkyl-, (C₃-C₈ cycloalkenyloxy)alkyl- or    (heterocycloalkyloxy)alkyl-, wherein the heteroatom of each of said    heteroaryl and heterocycloalkyl numbers 1, 2 or 3, and is    independently selected from N, S or O, further wherein each of said    aryl, heteroaryl and heterocycloalkyl may independently be either    substituted or fused with an aryl or heteroaryl, still further    wherein any of said aryl, heteroaryl and heterocycloalkyl is either    unsubstituted or optionally independently substituted with one or    more substituents which can be the same or different and are    independently selected from the group consisting of deuterium, halo,    cyano, amino, aminoalkyl-, (amino)alkoxy-, —CONH₂, —C(O)NH(alkyl),    —C(O)N(alkyl)₂, —C(O)NH(aryl), —C(O)N(aryl)₂, —CH_(z)F_(3−z),    —OCH_(z)F_(3−z), -alkyl, -alkenyl, -alkynyl, -alkoxy, hydroxyl,    alkyl hydroxy, hydroxyl, alkyl hydroxy, or (alkoxyalkyl) amino-,    —N(R³)—C(O)-alkyl, —N(R³)—C(O)-aryl, -cycloalkyl, -heterocycloalkyl,    -aryl, and heteroaryl, with the proviso that no two adjacent ring    heteroatoms are both S or both O;-   Ar is aryl, heteroaryl, heterocycloalkyl or C₃ to C₈ cycloalkyl,    with each of said aryl, heteroaryl, heterocycloalkyl and cycloalkyl    being either unsubstituted or optionally independently substituted    with 1, 2, 3 or 4 substituents which can be the same or different    and are independently selected from the group consisting of    deuterium, halo, cyano, amino, aminoalkyl-, (amino)alkoxy-, —CONH₂,    —C(O)NH(alkyl), —C(O)N(alkyl)₂, —C(O)NH(aryl), —C(O)N(aryl)₂,    —CH_(z)F_(3−z), —OCH_(z)F_(3−z), -alkyl, -alkenyl, -alkynyl,    -alkoxy, hydroxyl, -alkyl hydroxyl, aryloxy-, (alkoxyalkyl)amino-,    —N(R³)—C(O)-alkyl, —N(R³)—C(O)-aryl, -cycloalkyl, -heterocycloalkyl,    -aryl, and -heteroaryl;-   R⁴ is cycloalkyl, —CH_(z)F_(3−z), aryl, heterocycloalkyl,    heteroaryl, alkyl, -alkenyl, -alkynyl, (aryl)alkyl-,    (heteroaryl)alkyl- or (heterocycloalkyl)alkyl-, or

-   (i) wherein each of said cycloalkyl, aryl, heterocycloalkyl,    heteroaryl and alkyl is either unsubstituted or optionally    substituted with 1, 2, 3, 4 or 5 substituents which can be the same    or different and are independently selected from the group    consisting of deuterium, halo, cyano, amino, aminoalkyl-,    (amino)alkoxy-, —CONH₂, —C(O)NH(alkyl), —C(O)N(alkyl)₂,    —C(O)NH(aryl), —C(O)N(aryl)₂, —CH_(z)F_(3−z), —OCH_(z)F_(3−z),    -alkyl, alkoxy-, -alkenyl, -alkynyl, aryloxy-, (alkoxyalkyl)amino-,    -cycloalkyl, -heterocycloalkyl, (heterocycloalkyl)alkyl-, -aryl,    (aryl)alkyl-, -heteroaryl, (heteroaryl)alkyl-, —S(O)₂-alkyl,    —S(O)₂-aryl, —S(O)₂—CF₃, —C(O)N(alkyl)₂, —C(O)alkyl,    —N(R³)—C(O)-alkyl, —N(R³)—C(O)-aryl, —S(O₂)NH₂, —S(O₂)NH(alkyl),    —S(O₂)N(alkyl)₂, —N(H)S(O₂)(alkyl), —C(O)N(H)(alkyl), and    methylenedioxy, (ii) further wherein each of said cycloalkyl, aryl,    heterocycloalkyl, and heteroaryl may optionally additionally be    fused with independently selected aryl, heteroaryl, heterocycloalkyl    or cycloalkyl;-   R³ is H, alkyl or arylalkyl-;-   X is S, S(O), S(O)₂, O or C(O);-   n is 1, 2, 3 or 4;-   m is 0, 1, 2, 3 or 4;-   q is 0 or 1;-   t is 0, 1 or 2; and-   z is 0, 1 or 2;-   and pharmaceutically acceptable salts, solates, esters, prodrugs and    isomers thereof.

Another aspect of the invention are the compounds of Formula I, whereq=0, m=0, t=0, A=Ar, X=Q and R⁴ is

and the formula is now Formula IB

where:

-   R and R³ are as defined in Formula I;-   R¹ and R² are the same or they are different, and are independently    selected from H, a straight or branched C₁ to C₇ alkyl, straight or    branched C₁ to C₇ alkoxy, straight or branched C₁ to C₄    hydroxyalkyl, aryl, heteroaryl, heterocycloalkyl and cycloalkyl, and    wherein heteroatoms of said heteroaryl and heterocycloalkyl are    independently selected from one or more N, O and S, with the proviso    that no two adjacent ring heteroatoms are both S or both O, further    wherein R¹ and R² can be either unsubstituted or optionally    independently substituted with one or more substituents which can be    the same or different and are independently selected from the group    consisting of deuterium, halo, cyano, amino, aminoalkyl-,    (amino)alkoxy-, —CONH₂, —C(O)NH(alkyl), —C(O)N(alkyl)₂,    —C(O)NH(aryl), —C(O)N(aryl)₂, —CH_(z)F_(3−z), —OCH_(z)F_(3−z),    -alkyl, -alkenyl, -alkynyl, hydroxyalkyl-, -alkoxy, hydroxyl, alkyl    hydroxy, carboxy, (alkoxyalkyl) amino-, -alkylamine, aminocarbonyl-,    —CHO, —N(R³)—C(O)-alkyl, —N(R³)—C(O)-aryl, -cycloalkyl,    -heterocycloalkyl, -aryl, and heteroaryl;-   A is aryl, heteroaryl, heterocycloalkyl or C₃ to C₈ cycloalkyl, with    each of said aryl, heteroaryl, heterocycloalkyl and cycloalkyl being    either unsubstituted or optionally independently substituted with 1,    2, 3 or 4 substituents which can be the same or different and are    independently selected from the group consisting of deuterium, halo,    cyano, amino, aminoalkyl-, (amino)alkoxy-, —CONH₂, —C(O)NH(alkyl),    —C(O)N(alkyl)₂, —C(O)NH(aryl), —C(O)N(aryl)₂, —CH_(z)F_(3−z),    —OCH_(z)F_(3−z), -alkyl, -alkenyl, -alkynyl,-alkoxy, hydroxyl,    -alkyl hydroxyl, aryloxy-, (alkoxyalkyl)amino-, —N(R³)—C(O)-alkyl,    —N(R³)—C(O)-aryl, -cycloalkyl, -heterocycloalkyl, -aryl, and    -heteroaryl;-   Q is C(O), S(O), S(O)₂, —N(H)—C(O)—, —S(O₂)—NH—, or —N(H)—S(O₂)—;-   n is 0, 1, 2, 3 or 4; and-   z is 0, 1 or 2;-   and pharmaceutically acceptable salts, solvates, esters, prodrugs or    isomers thereof.

Another aspect of this invention is the provision of compounds,compositions, kits, and antidotes for the NAMPT pathway in mammalshaving a compound derived from Formula I where q=0, m=0 and t=0, wherebythe formula becomes Formula II or pharmaceutically acceptable saltsthereof:

where:

-   R is heteroaryl comprising 1, 2, 3 or 4 heteroatom(s) independently    selected from N, S or O, wherein said heteroaryl may be substituted    by one or more substituents selected from the group consisting of    amino, oxo, and halo; and wherein said heteroaryl can comprise one    or more N-oxide(s) formed with a N atom member of said heteroaryl;-   Ar is aryl or heteroaryl comprising 1, 2, 3 or 4 heteroatom(s)    independently selected from N, S or O;-   X is S(O)₂ or SO;-   R¹ is —NHR⁴ where R⁴ is cycloalkyl, heterocycloalkyl, aryl or    heteroaryl;    -   cycloalkyl;    -   aryl;    -   heterocycloalkyl; or    -   heteroaryl; wherein:        -   (i) each of said cycloalkyl, aryl, or heteroaryl is            unsubstituted or substituted with 1, 2, 3, 4 or 5            substituents which can be the same or different and are            independently selected from the group consisting of:            -   deuterium, halo, hydroxy, hydroxyalkyl, cyano,                —(CH₂)_(m)NR^(a)R^(b), oxo, alkyl, cyanoalkyl,                haloalkyl, alkoxy, haloalkoxy, alkoxyalkyl-, alkenyl,                alkynyl, alkynylalkoxy, —CONH₂, —S-alkyl,                —C(O)NH(alkyl), —C(O)N(alkyl)₂, —C(O)NH(cycloalkyl),                —C(O)NH(aryl), —C(O)N(aryl)₂, arylalkyl-, arylalkoxy-,                aryloxy-, cycloalkyl, heterocycloalkyl, aryl,                (heterocycloalkyl)alkyl-, (heterocycloalkyl)alkoxy-,                —C(O)heterocycloalkyl, heteroaryl, (heteroaryl)alkyl-,                —S(O)₂-alkyl, —S(O)₂-aryl, —S(O)₂—CH_(z)F_(3−z),                —C(O)alkyl, —N(R⁵)—C(O)-alkyl, —N(R⁵)—C(O)-aryl,                —S(O₂)NH₂, —S(O₂)NH(alkyl), —S(O₂)N(alkyl)₂,                —N(H)(SO₂)(alkyl), and methylenedioxy, wherein each of                said cycloalkyl, heterocycloalkyl, aryl or heteroaryl                may be substituted by one or more halo, cyano, alkyl or                alkoxy and;        -   (ii) each of said cycloalkyl, heterocycloalkyl, aryl, or            heteroaryl may optionally additionally be fused with            independently selected aryl, heteroaryl, heterocycloalkyl or            cycloalkyl to from a bicyclic or tricyclic group that may be            substituted by one or more halo, cyano, alkyl or alkoxy;-   R² and R³ can be independently selected from the group consisting of    H and deuterium;-   R⁵ is H, alkyl or arylalkyl-;-   R^(a) and R^(b) are independently selected from the group consisting    of H, alkyl, alkoxy, alkoxyalkyl and haloalkyl;-   m is 0, 1, 2, 3, 4, 5 or 6; and-   n is 0 or 1.

Another aspect of this invention are compounds Formula II orpharmaceutically acceptable salts thereof where X=SO₂, and the formulais:

where:

-   R is heteroaryl comprising 1, 2, 3 or 4 heteroatom(s) independently    selected from N, S or O, wherein said heteroaryl may be substituted    by one or more substituents selected from the group consisting of    amino, oxo, and halo; and wherein said heteroaryl can comprise one    or more N-oxide(s) formed with a N atom member of said heteroaryl;-   Ar is aryl or 5 or 6 membered heteroaryl comprising 1, 2, 3 or 4    heteroatom(s) independently selected from N, S or O;-   R¹ is —NHR⁴ and R⁴ is cycloalkyl, heterocycloalkyl, aryl or    heteroaryl;    -   cycloalkyl;    -   aryl; or    -   heteroaryl; wherein:    -   each of said cycloalkyl, aryl, or heteroaryl is unsubstituted or        substituted with 1, 2, 3, 4 or 5 substituents which can be the        same or different and are independently selected from the group        consisting of:        -   deuterium, halo, hydroxy, hydroxyalkyl, cyano,            —(CH₂)_(m)NR^(a)R^(b), oxo, alkyl, cyanoalkyl, haloalkyl,            alkoxy, haloalkoxy, alkoxyalkyl-, alkenyl, alkynyl,            alkynylalkoxy, —CONH₂, —S-alkyl, —C(O)NH(alkyl),            —C(O)N(alkyl)₂, —C(O)NH(cycloalkyl), —C(O)NH(aryl),            —C(O)N(aryl)₂, arylalkyl-, arylalkoxy-, aryloxy-,            cycloalkyl, heterocycloalkyl, aryl,            (heterocycloalkyl)alkyl-, (heterocycloalkyl)alkoxy-,            —C(O)heterocycloalkyl, heteroaryl, (heteroaryl)alkyl-,            —S(O)₂-alkyl, —S(O)₂-aryl, —S(O)₂—CH_(z)F_(3−z), —C(O)alkyl,            —N(R⁵)—C(O)-alkyl, —N(R⁵)—C(O)-aryl, —S(O₂)NH₂,            —S(O₂)NH(alkyl), —S(O₂)N(alkyl)₂, —N(H)(SO₂)(alkyl), and            methylenedioxy, wherein each of said cycloalkyl,            heterocycloalkyl, aryl or heteroaryl may be            -   substituted by one or more halo, cyano, alkyl or alkoxy                and;    -   each of said cycloalkyl, heterocycloalkyl, aryl, or heteroaryl        may optionally additionally be fused with independently selected        aryl, heteroaryl, heterocycloalkyl or cycloalkyl to from a        bicyclic or tricyclic group that may be substituted by one or        more halo, cyano, alkyl or alkoxy;-   R² and R³ can be independently selected from the group consisting of    H and deuterium;-   R⁵ is H, alkyl or arylalkyl-;-   R^(a) and R^(b) are independently selected from the group consisting    of H, alkyl, alkoxy, alkoxyalkyl and haloalkyl;and    -   m is 0, 1, 2, 3, 4, 5 or 6.

Yet another aspect of the invention is compounds of Formula IIA, whereAr=phenyl, whereby the formula becomes Formula IIB: We claim:

where:

-   R is bicyclic heteroaryl comprising 1, 2, 3 or 4 heteroatom(s)    independently selected from N, S or O, wherein said heteroaryl may    be substituted by one or more substituents selected from the group    consisting of amino, oxo, and halo; and wherein said heteroaryl can    comprise one or more N-oxide(s) formed with a N atom member of said    heteroaryl;-   R¹ is —NHR⁴ and R⁴ is cycloalkyl, heterocycloalkyl, aryl or    heteroaryl;    -   cycloalkyl;    -   aryl; or    -   heteroaryl; wherein:    -   each of said cycloalkyl, aryl, or heteroaryl is unsubstituted or        substituted with 1, 2, 3, 4 or 5 substituents which can be the        same or different and are independently selected from the group        consisting of:        -   deuterium, halo, hydroxy, hydroxyalkyl, cyano,            —(CH₂)_(m)NR^(a)R^(b), oxo, alkyl, cyanoalkyl, haloalkyl,            alkoxy, haloalkoxy, alkoxyalkyl-, alkenyl, alkynyl,            alkynylalkoxy, —CONH₂, —S-alkyl, —C(O)NH(alkyl),            —C(O)N(alkyl)₂, —C(O)NH(cycloalkyl), —C(O)NH(aryl),            —C(O)N(aryl)₂, arylalkyl-, arylalkoxy-, aryloxy-,            cycloalkyl, heterocycloalkyl, aryl,            (heterocycloalkyl)alkyl-, (heterocycloalkyl)alkoxy-,            —C(O)heterocycloalkyl, heteroaryl, (heteroaryl)alkyl-,            —S(O)₂-alkyl, —S(O)₂-aryl, —S(O)₂—CH_(z)F_(3−z), —C(O)alkyl,            —N(R⁵)—C(O)-alkyl, —N(R⁵)—C(O)-aryl, —S(O₂)NH₂,            —S(O₂)NH(alkyl), —S(O₂)N(alkyl)₂, —N(H)(SO₂)(alkyl), and            methylenedioxy, wherein each of said cycloalkyl,            heterocycloalkyl, aryl or heteroaryl may be substituted by            one or more halo, cyano, alkyl or alkoxy and;    -   each of said cycloalkyl, heterocycloalkyl, aryl, or heteroaryl        may optionally additionally be fused with independently selected        aryl, heteroaryl, heterocycloalkyl or cycloalkyl to from a        bicyclic or tricyclic group that may be substituted by one or        more halo, cyano, alkyl or alkoxy;-   R² and R³ can be independently selected from the group consisting of    H and deuterium;-   R⁵ is H, alkyl or arylalkyl-;-   R^(a) and R^(b) are independently selected from the group consisting    of H, alkyl, alkoxy, alkoxyalkyl and haloalkyl;-   m is 0, 1, 2, 3, 4, 5 or 6;-   z is 0, 1 or 2.

Another aspect of this invention is the provision of methods of treatinga disease via the inhibition of NAMPT in a subject (e.g., a human) inneed thereof by administering to the subject an effective amount of thecompound or the pharmaceutical formulation of the present invention.

Still another aspect of this invention is to provide a method fortreating, preventing, inhibiting or eliminating a disease or conditionin a patient by inhibiting NAMPT in said patient by administering atherapeutically effective amount of at least one compound of thisdisclosure, wherein said disease or condition is selected from the groupconsisting of cancer, ovarian cancer, breast cancer, uterine cancer,colon cancer, cervical cancer, lung cancer, prostate cancer, skincancer, bladder cancer, pancreatic cancer, leukemia, lymphoma, Hodgkin'sdisease, viral infections, Human Immunodeficiency Virus, hepatitisvirus, herpes virus, herpes simplex, inflammatory disorders, irritablebowel syndrome, inflammatory bowel disease, rheumatoid arthritis,asthma, chronic obstructive pulmonary disease, osteoarthritis,osteoporosis, dermatitis, atoptic dermatitis, psoriasis, systemic lupuserythematosis, multiple sclerosis, psoriatic arthritis, ankylosingspodylitis, graft-versus-host disease, Alzheimer's disease,cerebrovascular accident, atherosclerosis, diabetes,glomerulonephiritis, metabolic syndrome, non-small cell lung cancer,small cell lung cancer, multiple myeloma, leukemias, lymphomas, squamouscell cancers, kidney cancer, uretral and bladder cancers, cancers ofhead and neck, cancers of the brain and central nervous system.

Another preferred embodiment is a pharmaceutical formulation comprisinga pharmaceutically acceptable compound of the present invention, whichprovides, upon administration to a human, a decrease in tumor burdenand/or metastases. The pharmaceutical formulation can be administered byoral means or other suitable means.

Yet another embodiment is a method of treating ovarian cancer in asubject (e.g., a human) in need thereof by administering to the subjectan effective amount of the compound or the pharmaceutical formulation ofthe present invention.

Yet another embodiment is a method of treating colon cancer in a subject(e.g., a human) in need thereof by administering to the subject aneffective amount of the compound or the pharmaceutical formulation ofthe present invention.

Yet another embodiment is a method of treating breast cancer in asubject (e.g., a human) in need thereof by administering to the subjectan effective amount of the pharmaceutical formulation of the presentinvention.

Yet another embodiment is a method of treating leukemia in a subject(e.g., a human) in need thereof by administering to the subject aneffective amount of the compound or the pharmaceutical formulation ofthe present invention.

Yet another embodiment is a method of treating colon cancer before orafter surgical resection and/or radiation therapy, in a subject (e.g., ahuman) in need thereof by administering to the subject an effectiveamount of the compound or the pharmaceutical formulation of the presentinvention.

Yet another embodiment is a method of treating cancer before or aftersurgical resection and/or radiation therapy, in a subject (e.g., ahuman) in need thereof by administering to the subject an effectiveamount of the compound or the pharmaceutical formulation of the presentinvention, including adjunctive therapy to treat nausea, with or withoutdexamethasone.

Yet another embodiment is a method of treating cancer before or aftersurgical resection and or radiation therapy, in a subject (e.g., ahuman) in need thereof by administering to the subject an effectiveamount of the compound or the pharmaceutical formulation of the presentinvention, including adjunctive therapy with one or more additionaltherapeutic agents, or their pharmaceutically acceptable salts.Non-limiting examples of such additional therapeutic agents includecytotoxic agents (such as for example, but not limited to, DNAinteractive agents (such as cisplatin or doxorubicin)); taxanes (e.g.taxotere, taxol); topoisomerase II inhibitors (such as etoposide);topoisomerase I inhibitors (such as irinotecan (or CPT-11), camptostar,or topotecan); tubulin interacting agents (such as paclitaxel, docetaxelor the epothilones); hormonal agents (such as tamoxifen); thymidilatesynthase inhibitors (such as 5-fluorouracil or 5-FU); anti-metabolites(such as methoxtrexate); alkylating agents (such as temozolomide,cyclophosphamide); Farnesyl protein transferase inhibitors (such as,SARASAR™.(4-[2-[4-[(11R)-3,10-dibromo-8-chloro-6,11-dihydro-5H-benzo[5,-6]cyclohepta[1,2-b]pyridin-11-yl-]-1-piperidinyl]-2-oxoehtyl]-1-piperidine-carboxamide,or SCH 66336), tipifarnib (Zarnestra® or R115777 from JanssenPharmaceuticals), L778,123 (a farnesyl protein transferase inhibitorfrom Merck & Company, Whitehouse Station, N.J.), BMS 214662 (a farnesylprotein transferase inhibitor from Bristol-Myers Squibb Pharmaceuticals,Princeton, N.J.); signal transduction inhibitors (such as, Iressa® (fromAstra Zeneca Pharmaceuticals, England), Tarceva® (EGFR kinaseinhibitors), antibodies to EGFR (e.g., C225), GLEEVEC® (C-abl kinaseinhibitor from Novartis Pharmaceuticals, East Hanover, N.J.);interferons such as, for example, intron® (from Merck & Company),Peg-Intron® (from Merck & Company); hormonal therapy combinations;aromatase combinations; ara-C, adriamycin, cytoxan, and gemcitabine.

Other anti-cancer (also known as anti-neoplastic) agents include but arenot limited to Uracil mustard, Chlormethine, Ifosfamide, Melphalan,Chlorambucil, Pipobroman, Triethylenemelamine,Triethylenethiophosphoramine, Busulfan, Carmustine, Lomustine,Streptozocin, Dacarbazine, Floxuridine, Cytarabine, 6-Mercaptopurine,6-Thioguanine, Fludarabine phosphate, oxaliplatin, leucovirin,oxaliplatin (ELOXATIN® from Sanofi-Synthelabo Pharmaceuticals, France),Pentostatine, Vinblastine, Vincristine, Vindesine, Bleomycin,Dactinomycin, Daunorubicin, Doxorubicin, Epirubicin, Idarubicin,Mithramycin, Deoxycoformycin, Mitomycin-C, L-Asparaginase, Teniposide17a-Ethinylestradiol, Diethylstilbestrol, Testosterone, Prednisone,Fluoxymesterone, Dromostanolone propionate, Testolactone,Megestrolacetate, Methylprednisolone, Methyltestosterone, Prednisolone,Triamcinolone, Chlorotrianisene, Hydroxyprogesterone, Aminoglutethimide,Estramustine, Medroxyprogesteroneacetate, Leuprolide, Flutamide,Toremifene, goserelin, Cisplatin, Carboplatin, Hydroxyurea, Amsacrine,Procarbazine, Mitotane, Mitoxantrone, Levamisole, Navelbene,Anastrazole, Letrazole, Capecitabine, Reloxafine, Droloxafine,Hexamethylmelamine, Avastin, herceptin, Bexxar, Velcade®, Zevalin,Trisenox, Xeloda, Vinorelbine, Porfimer, Erbitux, Liposomal, Thiotepa,Altretamine, Melphalan, Trastuzumab, Lerozole, Fulvestrant, Exemestane,Ifosfomide, Rituximab, C225, and Campath, 5-fluorouracil and leucovorin,with or without a 5-HT₃ receptor inhibitor (e.g., dolansetron,granisetron, ondansetron) with or without dexamethasone.

If formulated as a fixed dose, such combination products employ thecompounds of this invention within the dosage range described herein (oras known to those skilled in the art) and the other pharmaceuticallyactive agents or treatments within its dosage range. For example, theCDC2 inhibitor olomucine has been found to act synergistically withknown cytotoxic agents in inducing apoptosis (J. Cell Sci., (1995) 108,2897). The compounds of the invention may also be administeredsequentially with known anticancer or cytotoxic agents when acombination formulation is inappropriate. In any combination treatment,the invention is not limited in the sequence of administration;compounds of the disclosed Formulas may be administered either prior toor after administration of the known anticancer or cytotoxic agent. Forexample, the cytotoxic activity of the cyclin-dependent kinase inhibitorflavopiridol is affected by the sequence of administration withanticancer agents. Cancer Research, (1997) 57, 3375. Such techniques arcwithin the skills of persons skilled in the art as well as attendingphysicians.

Any of the aforementioned methods may be augmented by administration offluids (such as water), loop diuretics, one or more of achemotherapeutic or antineoplastic agent, such as leucovorin andfluorouracil, and an adjunctive chemotherapeutic agent (such asfilgrastim and erythropoietin), or any combination of the foregoing.

Yet another embodiment is a method for administering a compound of theinstant invention to a subject (e.g., a human) in need thereof byadministering to the subject the pharmaceutical formulation of thepresent invention.

Yet another embodiment is a method of preparing a pharmaceuticalformulation of the present invention by mixing at least onepharmaceutically acceptable compound of the present invention, and,optionally, one or more pharmaceutically acceptable additives orexcipients.

For preparing pharmaceutical compositions from the compounds describedby this invention, inert, pharmaceutically acceptable carriers can beeither solid or liquid. Solid form preparations include powders,tablets, dispersible granules, capsules, cachets and suppositories. Thepowders and tablets may be comprised of from about 5 to about 95 percentactive ingredient. Suitable solid carriers are known in the art, e.g.,magnesium carbonate, magnesium stearate, talc, sugar or lactose.Tablets, powders, cachets and capsules can be used as solid dosage formssuitable for oral administration. Examples of pharmaceuticallyacceptable carriers and methods of manufacture for various compositionsmay be found in A. Gennaro (ed.), Remington's Pharmaceutical Sciences,18th Edition, (1990), Mack Publishing Co., Easton, Pa.

Liquid form preparations include solutions, suspensions and emulsions.As an example may be mentioned water or water-propylene glycol solutionsfor parenteral injection or addition of sweeteners and opacifiers fororal solutions, suspensions and emulsions. Liquid form preparations mayalso include solutions for intranasal administration.

Aerosol preparations suitable for inhalation may include solutions andsolids in powder form, which may be in combination with apharmaceutically acceptable carrier, such as an inert compressed gas,e.g. nitrogen.

Also included arc solid form preparations that arc intended to beconverted, shortly before use, to liquid form preparations for eitheroral or parenteral administration. Such liquid forms include solutions,suspensions and emulsions.

The compounds of the invention may also be deliverable transdermally.The transdermal compositions can take the form of creams, lotions,aerosols and/or emulsions and can be included in a transdermal patch ofthe matrix or reservoir type as are conventional in the art for thispurpose.

The compounds of this invention may also be delivered subcutaneously.

Preferably the compound is administered orally or intravenously.

Preferably, the pharmaceutical preparation is in a unit dosage form. Insuch form, the preparation is subdivided into suitably sized unit dosescontaining appropriate quantities of the active component, e.g., aneffective amount to achieve the desired purpose.

The quantity of active compound in a unit dose of preparation may bevaried or adjusted from about 1 mg to about 1000 mg, preferably fromabout 1 mg to about 500 mg, more preferably from about 1 mg to about 250mg, still more preferably from about 1 mg to about 25 mg, according tothe particular application.

The actual dosage employed may be varied depending upon the requirementsof the patient and the severity of the condition being treated.Determination of the proper dosage regimen for a particular situation iswithin the skill of the art. For convenience, the total daily dosage maybe divided and administered in portions during the day as required.

The amount and frequency of administration of the compounds of theinvention and/or the pharmaceutically acceptable salts thereof will beregulated according to the judgment of the attending clinicianconsidering such factors as age, condition and size of the patient aswell as severity of the symptoms being treated. A typical recommendeddaily dosage regimen for oral administration can range from about 1mg/day to about 500 mg/day, preferably 1 mg/day to 200 mg/day, in two tofour divided doses.

Definitions

As used above, and throughout this disclosure, the following terms,unless otherwise indicated, shall be understood to have the followingmeanings. If a definition is missing, convention definition as known toone skilled in the art controls.

“Patient” includes both human and animals.

“Mammal” means humans and other mammalian animals.

The term “inhibitor” refers to a molecule such as a compound, a drug, anenzyme activator or a hormone that blocks or otherwise interferes with aparticular biologic activity.

The terms “effective amount” or “therapeutically effective amount” referto a sufficient amount of the agent to provide the desired biologicalresult. That result can be reduction and/or alleviation of the signs,symptoms, or causes of a disease, or any other desired alteration of abiological system. For example, an “effective amount” for therapeuticuse is the amount of the composition comprising a compound as disclosedherein required to provide a clinically significant decrease in adisease. An appropriate “effective” amount in any individual case may bedetermined by one of ordinary skill in the art using routineexperimentation. Thus, the expression “effective amount” generallyrefers to the quantity for which the active substance has therapeuticeffects. In the present case the active substance is the inhibitor ofthe formation of Nicotinamide phosphoribosyltransferase (NAMPT).

As used herein, the terms “treat” or “treatment” are synonymous with theterm “prevent” and are meant to indicate a postponement of developmentof diseases, preventing the development of diseases, and/or reducingseverity of such symptoms that will or are expected to develop. Thus,these terms include ameliorating existing disease symptoms, preventingadditional symptoms, ameliorating or preventing the underlying metaboliccauses of symptoms, inhibiting the disorder or disease, e.g., arrestingthe development of the disorder or disease, relieving the disorder ordisease, causing regression of the disorder or disease, relieving acondition caused by the disease or disorder, or stopping the symptoms ofthe disease or disorder.

By “pharmaceutically acceptable” or “pharmacologically acceptable” ismeant a material which is not biologically or otherwise substantiallyundesirable, i.e., the material may be administered to an individualwithout causing any substantially undesirable biological effects orinteracting in a substantially deleterious manner with any of thecomponents of the composition in which it is contained. Exemplary saltsinclude, but are not limited, to sulfate, citrate, acetate, oxalate,chloride, bromide, iodide, nitrate, bisulfate, phosphate, acidphosphate, isonicotinate, lactate, salicylate, acid citrate, tartrate,oleate, tannate, pantothenate, bitartrate, ascorbate, succinate,maleate, gentisinate, fumarate, gluconate, glucuronate, saccharate,formate, benzoate, glutamate, methanesulfonate “mesylate”,ethanesulfonate, benzenesulfonate, p-toluenesulfonate, and pamoate(i.e., 1,1′-methylene-bis(2-hydroxy-3-naphthoate)) salts. Apharmaceutically acceptable salt may involve the inclusion of anothermolecule such as an acetate ion, a succinate ion or other counter ion.The counter ion may be any organic or inorganic moiety that stabilizesthe charge on the parent compound. Furthermore, a pharmaceuticallyacceptable salt may have more than one charged atom in its structure.Instances where multiple charged atoms are part of the pharmaceuticallyacceptable salt can have multiple counter ions. Hence, apharmaceutically acceptable salt can have one or more charged atomsand/or one or more counter ion.

“Carrier materials” or what are also referred to as “excipients” includeany commonly used excipients in pharmaceutics and should be selected onthe basis of compatibility and the release profile properties of thedesired dosage form. Exemplary carrier materials include, e.g., binders,suspending agents, disintegration agents, filling agents, surfactants,solubilizers, stabilizers, lubricants, wetting agents, diluents, and thelike. “Pharmaceutically compatible carrier materials” may comprise,e.g., acacia, gelatin, colloidal silicon dioxide, calciumglycerophosphate, calcium lactate, maltodextrin, glycerine, magnesiumsilicate, sodium caseinate, soy lecithin, sodium chloride, tricalciumphosphate, dipotassium phosphate, sodium stearoyl lactylate,carrageenan, monoglyceride, diglyceride, pregelatinized starch, and thelike. See, e.g., Hoover, John E., Remington's Pharmaceutical Sciences,Mack Publishing Co., Easton, Pa. 1975.

As used herein, the term “subject” encompasses mammals and non-mammals.Examples of mammals include, but are not limited to, any member of theMammalian class: humans, non-human primates such as chimpanzees, andother apes and monkey species; farm animals such as cattle, horses,sheep, goats, swine; domestic animals such as rabbits, dogs, and cats;laboratory animals including rodents, such as rats, mice and guineapigs, and the like. Examples of non-mammals include, but are not limitedto, birds, fish and the like. In one embodiment of the presentinvention, the mammal is a human.

As used herein, “alkyl” means a straight chain or branched saturatedchain having from 1 to 10 carbon atoms. Representative saturated alkylgroups include, but are not limited to, methyl, ethyl, n-propyl,isopropyl, 2-methyl-1-propyl, 2-methyl-2-propyl, 2-methyl-1-butyl,3-methyl-1-butyl, 2-methyl-3-butyl, 2,2-dimethyl-1-propyl,2-methyl-1-pentyl, 3-methyl-1-pentyl, 4-methyl-1-pentyl,2-methyl-2-pentyl, 3-methyl-2-pentyl, 4-methyl-2-pentyl,2,2-dimethyl-1-butyl, 3,3-dimethyl-1-butyl, 2-ethyl-1-butyl, butyl,isobutyl, t-butyl, n-pentyl, isopentyl, neopentyl, n-hexyl and the like,and longer alkyl groups, such as heptyl, and octyl and the like. Analkyl group can be unsubstituted or substituted. Alkyl groups containingthree or more carbon atoms may be straight, branched or cyclized. Asused herein, “lower alkyl” means an alkyl having from 1 to 6 carbonatoms.

As used herein, an “alkenyl group” includes an unbranched or branchedhydrocarbon chain having one or more double bonds therein. The doublebond of an alkenyl group can be unconjugated or conjugated to anotherunsaturated group. Illustrative alkenyl groups include, but are notlimited to, (C₂-C₈) alkenyl groups, such as ethylenyl, vinyl, allyl,butenyl, pentenyl, hexenyl, butadienyl, pentadienyl, hexadienyl,2-ethylhexenyl, 2-propyl-2-butenyl, 4-(2-methyl-3-butene)-pentenyl andthe like. An alkenyl group can be unsubstituted or substituted.

The term “hydroxyalkyl” denotes an alkyl group as defined above whereinat least one of the hydrogen atoms of the alkyl group is replaced by ahydroxy group. Examples of hydroxyalkyl include, but are not limited to,methyl, ethyl, propyl, isopropyl, isobutyl, sec-butyl, tert-butyl,pentyl or n-hexyl wherein one or more hydrogen atoms are replaced by OH,as well as those hydroxyalkyl groups specifically illustrated by theexamples herein below.

The term “cyanoalkyl” denotes an alkyl group as defined above wherein atleast one of the hydrogen atoms of the alkyl group is replaced by acyano (—CN) group.

As used herein, “alkynyl group” includes an unbranched or branchedhydrocarbon chain having one or more triple bonds therein. The triplebond of an alkynyl group can be unconjugated or conjugated to anotherunsaturated group. Suitable alkynyl groups include, but are not limitedto, (C₂-C₆) alkynyl groups, such as ethynyl, propynyl, butynyl,pentynyl, hexynyl, methylpropynyl, 4-methyl-1-butynyl,4-propyl-2-pentynyl, 4-butyl-2-hexynyl and the like. An alkynyl groupcan be unsubstituted or substituted.

The term “haloalkyl” denotes an alkyl group as defined above wherein atleast one of the hydrogen atoms of the alkyl group is replaced by ahalogen atom, preferably fluoro or chloro, most preferably fluoro.Examples of haloalkyl include, but are not limited to, methyl, ethyl,propyl, isopropyl, isobutyl, sec-butyl, tert-butyl, pentyl or n-hexylwherein one or more hydrogen atoms are replaced by Cl, F, Br or Iatom(s), as well as those haloalkyl groups specifically illustrated bythe examples herein below. Among the preferred haloalkyl groups aremonofluoro-, difluoro- or trifluoro-methyl, -ethyl or -propyl, forexample 3,3,3-trifluoropropyl, 2-fluoroethyl, 2,2,2-trifluoroethyl,fluoromethyl, trifluoromethyl.

The terms “trifluoromethyl,” “sulfonyl,” and “carboxyl” include CF₃,SO₂, and CO₂ H, respectively.

The term “oxo” means ═O-group;

The term “hydroxy” means an OH group;

The term “alkoxy” as used herein includes —O-(alkyl), wherein alkyl isdefined above.

The term “aminoalkyl” as used herein means a group having one or morenitrogen atoms and one or more alkyl groups as defined above on thenitrogen.

“Aralkyl” or “arylalkyl” means an aryl-alkyl-group in which the aryl andalkyl are as previously described. Preferred aralkyls comprise a loweralkyl group. Non-limiting examples of suitable aralkyl groups includebenzyl, 2-phenethyl and naphthalenylmethyl. The bond to the parentmoiety is through the alkyl.

“Heteroarylalkyl” means a heteroaryl moiety as defined herein linked viaan alkyl moiety (defined above) to a parent core. Non-limiting examplesof suitable heteroaryls include 2-pyridinylmethyl, quinolinylmethyl andthe like.

“Heterocyclylalkyl” means a heterocyclyl moiety as defined herein linkedvia an alkyl moiety (defined above) to a parent core. Non-limitingexamples of suitable heterocyclylalkyls include piperidinylmethyl,piperazinylmethyl and the like.

The term “bicyclic heteroaryl” means a structure having atoms arrangedin two rings fused together with at least two atoms common to each ring,and and at least one of the rings being a heteroaryl ring. Non limitingexamples of bicyclic heteroaryl comprise bicyclic heteroaryl groupscomprising 1, 2, 3 or 4 heteroatom(s) independently selected from N, Sor O.

It should also be noted that any carbon as well as heteroatom withunsatisfied valences in the text, schemes, examples and Tables herein isassumed to have the sufficient number of hydrogen atom(s) to satisfy thevalences.

When any variable (e.g., aryl, heterocycle, R², etc.) occurs more thanone time in any constituent or in the Formulas, its definition on eachoccurrence is independent of its definition at every other occurrence.

The term “N-oxide(s) formed with a N atom member of said heteroaryl”denotes a heterorayl group containing a nitrogen atom that forms aN-oxide. Illustrative and non limiting examples of such N-oxides are:

As used herein, the term “composition” is intended to encompass aproduct comprising the specified ingredients in the specified amounts,as well as any product which results, directly or indirectly, fromcombination of the specified ingredients in the specified amounts.

The term “deuterium” as used herein means a stable isotope of hydrogenhaving odd numbers of protons and neutrons.

The term “halo” as used herein means a substituent having at least onehalogen selected from fluorine, chlorine, bromine, and iodine.

The term “cyano” as used herein means a substituent having a carbon atomjoined to a nitrogen atom by a triple bond.

The term “amino” as used herein means a substituent containing at leastone nitrogen atom.

The term “(amino)alkoxy” as used herein means a substituent having atleast one amino group and at least one alkoxy group.

The term “aryloxy” as used herein means a substituent of the form Ar—O—where Ar is an aryl group as defined herein.

The term “methylenedioxy” as used herein means a functional group withthe structural formula —O—CH₂—O— which is connected to the molecule bytwo chemical bonds via the oxygens.

As used herein, “alkoxyalkyl” means -(alkyl)-O-(alkyl), wherein each“alkyl” is independently an alkyl group defined above.

The term “(alkoxyalkyl)amino” as used herein means a substituent havingat least one alkoxyalkyl group as defined above and at least one aminogroup as defined above.

The term “spiroheterocycloalkyl” as used herein means a spiro group(containing no heteroatom) linked in a spiro manner to aheterocycloalkyl group. A non-limiting example would be the moiety shownbelow:

The term “heterospiroheterocycloalkyl” as used herein means a spirogroup (containing a hetero atom such O, N or S) linked in a spiro mannerto a heterocycloalkyl group. A non-limiting example would be the moietyshown below:

“Aryl” means a monovalent aromatic hydrocarbon radical of 6-20 carbonatoms (C₆-C₂₀) derived by the removal of one hydrogen atom from a singlecarbon atom of a parent aromatic ring system. Some aryl groups arerepresented in the exemplary structures as “Ar”. Aryl includes bicyclicradicals comprising an aromatic ring fused to a saturated, partiallyunsaturated ring, or aromatic carbocyclic ring. Typical aryl groupsinclude, but are not limited to, radicals derived from benzene (phenyl),substituted benzenes, naphthalene, anthracene, biphenyl, indenyl,indanyl, 1,2-dihydronaphthalene, 1,2,3,4-tetrahydronaphthyl, and thelike. Aryl groups are optionally substituted independently with one ormore substituents described herein. Illustrative examples of aryl groupsinclude, but are not limited to phenyl, naphthalene and the followingmoieties:

and the like.

Illustrative substituted aryls include:

and the like.

As used herein, the term “heteroaryl” refers to a monocyclic, or fusedpolycyclic, aromatic heterocycle (ring structure having ring atomsselected from carbon atoms as well as nitrogen, oxygen, and/or sulfuratoms) having from 3 to 24 ring atoms per ring. The term “heteroaryl” asused herein also includes a monovalent aromatic radical of a 5-, 6-, or7-membered ring and includes fused ring systems (at least one of whichis aromatic) of 5-10 atoms containing at least one heteroatomindependently selected from nitrogen, oxygen, and sulfur. Examples ofheteroaryl groups include, but are not limited to pyridinyl, imidazolyl,imidazopyridinyl, pyrimidinyl, pyrazolyl, triazolyl, pyrazinyl,tetrazolyl, furyl, thienyl, isoxazolyl, thiazolyl, oxazolyl,isothiazolyl, pyrrolyl, quinolinyl, isoquinolinyl, indolyl,benzimidazolyl, benzofuranyl, cinnolinyl, indazolyl, indolizinyl,phthalazinyl, pyridazinyl, triazinyl, isoindolyl, pteridinyl, purinyl,oxadiazolyl, triazolyl, thiadiazolyl, thiadiazolyl, furazanyl,benzofurazanyl, benzothiophenyl, benzothiazolyl, benzoxazolyl,quinazolinyl, quinoxalinyl, naphthyridinyl, and furopyridinyl. Spiromoieties are also included within the scope of this definition.Heteroaryl groups may be optionally substituted independently with oneor more substituents described herein. 5 or 6 membered heteroaryl can beselected from the group consisting of optionally substituted pyridinyl,pyrimidinyl, thiazolyl, imidazolyl, oxazolyl, isoxazolyl, pyrazolyl,pyridinone and benzimidazolyl. In a certain embodiment, heteroaryl isbicyclic heteroaryl selected from benzothiazole, dihydronaphthyridine,dihydropyridopyrimidine, dihydropyrrolopyridine, furopyridine,imidazopyrazine, imidazopyrazole imidazopyridine, imidazopyrimidine,indazole, indole, isoquinoline, naphthyridine, pyrazolopyridine,pyrrolopyridine, tetrazolopyridine, tetrahydroimidazopyridine,tetrahydropyrazolopyridine, thiazolopyridine and thienopyridine. In aanother embodiment, heteroaryl is bicyclic heteroaryl selected from1H-pyrazolo[3,4-b]pyridine; 1,4,6,7-Tetrahydro-pyrazolo[4,3-c]pyridine;7,8-Dihydro-5H-pyrido[4,3-d]pyrimidine;5,7-Dihydro-pyrrolo[3,4-b]pyridine; 7,8-Dihydro-5H-[1,6]naphthyridine;1,4,6,7-Tetrahydro-imidazo[4,5-c]pyridine;1,8a-dihydroimidazo[1,2-a]pyridine; thieno[3,2-c]pyridine;1H-imidazo[1,2-b]pyrazole; 1H-pyrazolo[3,4-b]pyridine;furo[2,3-c]pyridine; 1H-pyrazolo[3,4-b]pyridine;1H-pyrrolo[3,2-c]pyridine; thieno[2,3-b]pyridine;imidazo[1,2-a]pyrimidine; furo[2,3-c]pyridine; isoquinoline;1H-indazole; imidazo[1,2-a]pyridine; thieno[2,3-c]pyridine;furo[2,3-c]pyridine; 1H-pyrrolo[2,3-c]pyridine; imidazo[1,2-a]pyrazine;1,3-benzothiazole; benzo[d]thiazole; 1H-pyrrolo[2,3-b]pyridine;[1,3]thiazolo[5,4-c]pyridine; [1,2,3,4]tetrazolo[1,5-a]pyridine;1,5-naphthyridine; 1H-indole; 1H-imidazo[4,5-c]pyridine; and1,6-naphthyridine.

By way of example and not limitation, carbon bonded heterocycles andheteroaryls are bonded at position 2, 3, 4, 5, or 6 of a pyridine,position 3, 4, 5, or 6 of a pyridazine, position 2, 4, 5, or 6 of apyrimidine, position 2, 3, 5, or 6 of a pyrazine, position 2, 3, 4, or 5of a furan, tetrahydrofuran, thiofuran, thiophene, pyrrole ortetrahydropyrrole, position 2, 4, or 5 of an oxazole, imidazole orthiazole, position 3, 4, or 5 of an isoxazole, pyrazole, or isothiazole,position 2 or 3 of an aziridine, position 2, 3, or 4 of an azetidine,position 2, 3, 4, 5, 6, 7, or 8 of a quinoline or position 1, 3, 4, 5,6, 7, or 8 of an isoquinoline. Further examples of carbon bondedheterocycles include 2-pyridyl, 3-pyridyl, 4-pyridyl, 5-pyridyl,6-pyridyl, 3-pyridazinyl, 4-pyridazinyl, 5-pyridazinyl, 6-pyridazinyl,2-pyrimidinyl, 4-pyrimidinyl, 5-pyrimidinyl, 6-pyrimidinyl, 2-pyrazinyl,3-pyrazinyl, 5-pyrazinyl, 6-pyrazinyl, 2-thiazolyl, 4-thiazolyl, or5-thiazolyl.

By way of example and not limitation, nitrogen bonded heterocycles andheteroaryls are bonded at position 1 of an aziridine, azetidine,pyrrole, pyrrolidine, 2-pyrroline, 3-pyrroline, imidazole,imidazolidine, 2-imidazoline, 3-imidazoline, pyrazole, pyrazoline,2-pyrazoline, 3-pyrazoline, piperidine, piperazine, indole, indoline,1H-indazole, position 2 of an isoindole, or isoindoline, position 4 of amorpholine, and position 9 of a carbazole, or 13-carboline. Still moretypically, nitrogen bonded heterocycles include 1-aziridyl, 1-azetedyl,1-pyrrolyl, 1-imidazolyl, 1-pyrazolyl, and 1-piperidinyl.

The term “bicyclic heteroaryl” means a structure having atoms arrangedin two rings fused together with at least two atoms common to each ring,and and at least one of the rings being a heteroaryl ring. Illustrativeexamples of bicyclic heteroaryls include but arc not limited to:

and the like.

Further examples of bicyclic heteroaryls include but are not limited to:

These bicyclic heteroaryl groups can be substituted as defined for Rherein.

As used herein, the terms “cycloalkyl” and “cycloalkenyl” refers to asaturated or partially saturated, monocyclic or fused or spiropolycyclic, carbocycle having from 3 to 24 ring atoms per ring.Illustrative examples of cycloalkyl and “cycloalkenyl” groups include,but are not limited to, the following moieties:

and the like.

As used herein, the term “heterocycloalkyl” refers to a monocyclic, orfused or spiro, polycyclic, ring structure that is saturated orpartially saturated and has from 3 to 24 ring atoms per ring selectedfrom C atoms and N, O, and/or S atoms. Illustrative examples ofheterocycloalkyl and substituted heterocycloalkyl groups include, butare not limited to:

and the like.

Numerical ranges, as used herein, are intended to include sequentialwhole numbers. For example, a range expressed as “from 0 to 4” wouldinclude 0, 1, 2, 3 and 4.

As used herein, the term “substituted” means that the specified group ormoiety bears one or more suitable substituents.

As used herein, the term “unsubstituted” means that the specified groupbears no substituents.

As used herein, the term “optionally substituted” means that thespecified group is unsubstituted or substituted by one or moresubstituents.

When a multifunctional moiety is shown, the point of attachment to thecore is indicated by a line. For e.g. (cycloalkyloxy)alkyl- refers toalkyl being the point of attachment to the core while cycloalkyl isattached to alkyl via the oxy group.

The expression “adjunctive chemotherapeutic agent” generally refers toagents which treat, alleviate, relieve, or ameliorate the side effectsof chemotherapeutic agents. Such agents include those which modify bloodcell growth and maturation. Examples of adjunctive chemotherapeuticagents include, but are not limited to, filgrastim and erythropoietin.Other such adjunctive chemotherapeutic agents include those whichinhibit nausea associated with administration of the chemotherapeuticagents, such as a 5-HT₃ receptor inhibitor (e.g., dolansetron,granisetron, or ondansetron), with or without dexamethasone.

The terms “chemotherapeutic agent” and “antineoplastic agent” generallyrefer to agents which treat, prevent, cure, heal, alleviate, relieve,alter, remedy, ameliorate, improve, or affect malignancies and theirmetastasis. Examples of such agents (also known as “antineoplasticagents”) include, but are not limited to, prednisone, fluorouracil(e.g., 5-fluorouracil (5-FU)), anastrozole, bicalutamide, carboplatin,cisplatin, chlorambucil, cisplatin, carboplatin, docetaxel, doxorubicin,flutamide, interferon-alpha, letrozole, leuprolide, megestrol,mitomycin, oxaliplatin, paclitaxel, plicamycin (Mithracin™), tamoxifen,thiotepa, topotecan, valrubicin, vinblastine, vincristine, and anycombination of any of the foregoing. Additional such agents aredescribed later.

“Nicotinamide phosphoribosyltransferase” also named NAMPT, NMPRT,NMPRTase or NAmPRTase, (International nomenclature: E.C. 2.4.2.12) is akey enzyme in nicotinamide adenyl dinucleotide (NAD) biosynthesis fromthe natural precursor nicotinamide.

It must be noted that, as used in the specification and the appendedclaims, the singular forms “a,” “an” and “the” include plural referentsunless the context clearly dictates otherwise.

When used as a therapeutic agent the inhibitors of the formation ofnicotinamide phosphoribosyltransferase (NAMPT) described herein may beadministered with one or more physiologically acceptable excipients. Aphysiologically acceptable carrier or excipient is a formulation towhich the compound can be added to dissolve it or otherwise facilitateits administration.

The dosage forms of the present invention, may contain a mixture of oneor more compounds of this invention, and may include additionalmaterials known to those skilled in the art as pharmaceuticalexcipients. Such pharmaceutical excipients include, for example, thefollowing: Stabilizing additives may be incorporated into the deliveryagent solution. With some drugs, the presence of such additives promotesthe stability and dispersibility of the agent in solution. Thestabilizing additives may be employed at a concentration ranging fromabout 0.1 and 5% (W/V), preferably about 0.5% (W/V). Suitable, butnon-limiting, examples of stabilizing additives include gum acacia,gelatin, methyl cellulose, polyethylene glycol, carboxylic acids andsalts thereof, and polylysine. The preferred stabilizing additives arcgum acacia, gelatin and methyl cellulose.

Acidifying agents (acetic acid, glacial acetic acid, citric acid,fumaric acid, hydrochloric acid, diluted hydrochloric acid, malic acid,nitric acid, phosphoric acid, diluted phosphoric acid, sulfuric acid,tartaric acid); Aerosol propellants (butane, dichlorodifluoro-methane,dichlorotetrafluoroethane, isobutane, propane,trichloromonofluoromethane); Air displacements (carbon dioxide,nitrogen); Alcohol denaturants (denatonium benzoate, methyl isobutylketone, sucrose octacetate); Alkalizing agents (strong ammonia solution,ammonium carbonate, diethanolamine, diisopropanolamine, potassiumhydroxide, sodium bicarbonate, sodium borate, sodium carbonate, sodiumhydroxide, trolamine); Anticaking agents (see glidant); Antifoamingagents (dimethicone, simethicone); Antimicrobial preservatives(benzalkonium chloride, benzalkonium chloride solution, benzelthoniumchloride, benzoic acid, benzyl alcohol, butylparaben, cetylpyridiniumchloride, chlorobutanol, chlorocresol, cresol, dehydroacetic acid,ethylparaben, methylparaben, methylparaben sodium, phenol, phenylethylalcohol, phenylmercuric acetate, phenylmercuric nitrate, potassiumbenzoate, potassium sorbate, propylparaben, propylparaben sodium, sodiumbenzoate, sodium dehydroacetate, sodium propionate, sorbic acid,thimerosal, thymol); Antioxidants (ascorbic acid, acorbyl palmitate,butylated hydroxyanisole, butylated hydroxytoluene, hypophosphorousacid, monothioglycerol, propyl gallate, sodium formaldehyde sulfoxylate,sodium metabisulfite, sodium thiosulfate, sulfur dioxide, tocopherol,tocopherols excipient); Buffering agents (acetic acid, ammoniumcarbonate, ammonium phosphate, boric acid, citric acid, lactic acid,phosphoric acid, potassium citrate, potassium metaphosphate, potassiumphosphate monobasic, sodium acetate, sodium citrate, sodium lactatesolution, dibasic sodium phosphate, monobasic sodium phosphate); Capsulelubricants (see tablet and capsule lubricant); Chelating agents (edetatedisodium, ethylenediaminetetraacetic acid and salts, edetic acid);Coating agents (sodium carboxymethylcellulose, cellulose acetate,cellulose acetate phthalate, ethylcellulose, gelatin, pharmaceuticalglaze, hydroxypropyl cellulose, hydroxypropyl methylcellulose,hydroxypropyl methylcellulose phthalate, methacrylic acid copolymer,methylcellulose, polyethylene glycol, polyvinyl acetate phthalate,shellac, sucrose, titanium dioxide, carnauba wax, microcystalline wax,zein); Colorants (caramel, red, yellow, black or blends, ferric oxide);Complexing agents (ethylenediaminetetraacetic acid and salts (EDTA),edetic acid, gentisic acid ethanolmaide, oxyquinoline sulfate);Desiccants (calcium chloride, calcium sulfate, silicon dioxide);Emulsifying and/or solubilizing agents (acacia, cholesterol,diethanolamine (adjunct), glyceryl monostearate, lanolin alcohols,lecithin, mono- and di-glycerides, monoethanolamine (adjunct), oleicacid (adjunct), oleyl alcohol (stabilizer), poloxamer, polyoxyethylene50 stearate, polyoxyl 35 caster oil, polyoxyl 40 hydrogenated castoroil, polyoxyl 10 oleyl ether, polyoxyl 20 cetostearyl ether, polyoxyl 40stearate, polysorbate 20, polysorbate 40, polysorbate 60, polysorbate80, propylene glycol diacetate, propylene glycol monostearate, sodiumlauryl sulfate, sodium stearate, sorbitan monolaurate, soritanmonooleate, sorbitan monopalmitate, sorbitan monostearate, stearic acid,trolamine, emulsifying wax); Filtering aids (powdered cellulose,purified siliceous earth); Flavors and perfumes (anethole, benzaldehyde,ethyl vanillin, menthol, methyl salicylate, monosodium glutamate, orangeflower oil, peppermint, peppermint oil, peppermint spirit, rose oil,stronger rose water, thymol, tolu balsam tincture, vanilla, vanillatincture, vanillin); Glidants and/or anticaking agents (calciumsilicate, magnesium silicate, colloidal silicon dioxide, talc);Humectants (glycerin, hexylene glycol, propylene glycol, sorbitol);Plasticizers (castor oil, diacetylated monoglycerides, diethylphthalate, glycerin, mono- and di-acetylated monoglycerides,polyethylene glycol, propylene glycol, triacetin, triethyl citrate);Polymers (e.g., cellulose acetate, alkyl celloloses,hydroxyalkylcelloloses, acrylic polymers and copolymers); Solvents(acetone, alcohol, diluted alcohol, amylene hydrate, benzyl benzoate,butyl alcohol, carbon tetrachloride, chloroform, corn oil, cottonseedoil, ethyl acetate, glycerin, hexylene glycol, isopropyl alcohol, methylalcohol, methylene chloride, methyl isobutyl ketone, mineral oil, peanutoil, polyethylene glycol, propylene carbonate, propylene glycol, sesameoil, water for injection, sterile water for injection, sterile water forirrigation, purified water); Sorbents (powdered cellulose, charcoal,purified siliceous earth); Carbon dioxide sorbents (barium hydroxidelime, soda lime); Stiffening agents (hydrogenated castor oil,cetostearyl alcohol, cetyl alcohol, cetyl esters wax, hard fat,paraffin, polyethylene excipient, stearyl alcohol, emulsifying wax,white wax, yellow wax); Suspending and/or viscosity-increasing agents(acacia, agar, alginic acid, aluminum monostearate, bentonite, purifiedbentonite, magma bentonite, carbomer 934p, carboxymethylcellulosecalcium, carboxymethylcellulose sodium, carboxymethylcellulose sodium12, carrageenan, microcrystalline and carboxymethylcellulose sodiumcellulose, dextrin, gelatin, guar gum, hydroxyethyl cellulose,hydroxypropyl cellulose, hydroxypropyl methylcellulose, magnesiumaluminum silicate, methylcellulose, pectin, polyethylene oxide,polyvinyl alcohol, povidone, propylene glycol alginate, silicon dioxide,colloidal silicon dioxide, sodium alginate, tragacanth, xanthan gum);Sweetening agents (aspartame, dextrates, dextrose, excipient dextrose,fructose, mannitol, saccharin, calcium saccharin, sodium saccharin,sorbitol, solution sorbitol, sucrose, compressible sugar, confectioner'ssugar, syrup); Tablet binders (acacia, alginic acid, sodiumcarboxymethylcellulose, microcrystalline cellulose, dextrin,ethylcellulose, gelatin, liquid glucose, guar gum, hydroxypropylmethylcellulose, methycellulose, polyethylene oxide, povidone,pregelatinized starch, syrup); Tablet and/or capsule diluents (calciumcarbonate, dibasic calcium phosphate, tribasic calcium phosphate,calcium sulfate, microcrystalline cellulose, powdered cellulose,dextrates, dextrin, dextrose excipient, fructose, kaolin, lactose,mannitol, sorbitol, starch, pregelatinized starch, sucrose, compressiblesugar, confectioner's sugar); Tablet disintegrants (alginic acid,microcrystalline cellulose, croscarmellose sodium, corspovidone,polacrilin potassium, sodium starch glycolate, starch, pregelatinizedstarch); Tablet and/or capsule lubricants (calcium stearate, glycerylbehenate, magnesium stearate, light mineral oil, polyethylene glycol,sodium stearyl fumarate, stearic acid, purified stearic acid, talc,hydrogenated vegetable oil, zinc stearate); Tonicity agent (dextrose,glycerin, mannitol, potassium chloride, sodium chloride); Vehicle:flavored and/or sweetened (aromatic elixir, compound benzaldehydeelixir, iso-alcoholic elixir, peppermint water, sorbitol solution,syrup, tolu balsam syrup); Vehicle: oleaginous (almond oil, corn oil,cottonseed oil, ethyl oleate, isopropyl myristate, isopropyl palmitate,mineral oil, light mineral oil, myristyl alcohol, octyldodecanol, oliveoil, peanut oil, persic oil, seame oil, soybean oil, squalane); Vehicle:solid carrier (sugar spheres); Vehicle: sterile (bacteriostatic waterfor injection, bacteriostatic sodium chloride injection);Viscosity-increasing (see suspending agent); Water repelling agent(cyclomethicone, dimethicone, simethicone); and Wetting and/orsolubilizing agent (benzalkonium chloride, benzethonium chloride,cetylpyridinium chloride, docusate sodium, nonoxynol 9, nonoxynol 10,octoxynol 9, poloxamer, polyoxyl 35 castor oil, polyoxyl 40,hydrogenated castor oil, polyoxyl 50 stearate, polyoxyl 10 olcyl ether,polyoxyl 20, cetostearyl ether, polyoxyl 40 stearate, polysorbate 20,polysorbate 40, polysorbate 60, polysorbate 80, sodium lauryl sulfate,sorbitan monolaureate, sorbitan monooleate, sorbitan monopalmitate,sorbitan monostearate, tyloxapol). This list is not meant to beexclusive, but instead merely representative of the classes ofexcipients and the particular excipients which may be used in dosageforms of the present invention.

The compounds of the disclosed Formulas can form salts which are alsowithin the scope of this invention. Reference to a compound of theFormulas herein is understood to include reference to salts thereof,unless otherwise indicated. The term “salt(s)”, as employed herein,denotes acidic salts formed with inorganic and/or organic acids, as wellas basic salts formed with inorganic and/or organic bases. In addition,when a compound of the Formulas contains both a basic moiety, such as,but not limited to a pyridine or imidazole, and an acidic moiety, suchas, but not limited to a carboxylic acid, zwitterions (“inner salts”)may be formed and are included within the term “salt(s)” as used herein.Pharmaceutically acceptable (i.e., non-toxic, physiologicallyacceptable) salts are preferred, although other salts are also useful.Salts of the compounds of the Formulas may be formed, for example, byreacting a compound of Formulas with an amount of acid or base, such asan equivalent amount, in a medium such as one in which the saltprecipitates or in an aqueous medium followed by lyophilization.

Exemplary acid addition salts include acetates, ascorbates, benzoates,benzenesulfonates, bisulfates, borates, butyrates, citrates,camphorates, camphorsulfonates, fumarates, hydrochlorides,hydrobromides, hydroiodides, lactates, maleates, methanesulfonates,naphthalenesulfonates, nitrates, oxalates, phosphates, propionates,salicylates, succinates, sulfates, tartarates, thiocyanates,toluenesulfonates (also known as tosylates,) and the like. Additionally,acids which are generally considered suitable for the formation ofpharmaceutically useful salts from basic pharmaceutical compounds arediscussed, for example, by P. Stahl et al, Camille G. (eds.) Handbook ofPharmaceutical Salts. Properties, Selection and Use. (2002) Zurich:Wiley-VCH; S. Berge et al, Journal of Pharmaceutical Sciences (1977)66(1) 1-19; P. Gould, International J. of Pharmaceutics (1986) 33201-217; Anderson et al, The Practice of Medicinal Chemistry (1996),Academic Press, New York; and in The Orange Book (Food & DrugAdministration, MD, on their website). These disclosures arcincorporated herein by reference thereto.

Exemplary basic salts include ammonium salts, alkali metal salts such assodium, lithium, and potassium salts, alkaline earth metal salts such ascalcium and magnesium salts, salts with organic bases (for example,organic amines) such as dicyclohexylamines, t-butyl amines, and saltswith amino acids such as arginine, lysine and the like. Basicnitrogen-containing groups may be quartemized with agents such as loweralkyl halides (e.g. methyl, ethyl, and butyl chlorides, bromides andiodides), dialkyl sulfates (e.g. dimethyl, diethyl, and dibutylsulfates), long chain halides (e.g. decyl, lauryl, and stearylchlorides, bromides and iodides), aralkyl halides (e.g. benzyl andphenethyl bromides), and others.

All such acid salts and base salts are intended to be pharmaceuticallyacceptable salts within the scope of the invention and all acid and basesalts are considered equivalent to the free forms of the correspondingcompounds for purposes of the invention.

Pharmaceutically acceptable esters of the compounds of the invention arealso considered to be part of the invention. Pharmaceutically acceptableesters of the present compounds include the following groups: (1)carboxylic acid esters obtained by esterification of the hydroxy groups,in which the non-carbonyl moiety of the carboxylic acid portion of theester grouping is selected from straight or branched chain alkyl (forexample, acetyl, n-propyl, t-butyl, or n-butyl), alkoxyalkyl (forexample, methoxymethyl), aralkyl (for example, benzyl), aryloxyalkyl(for example, phenoxymethyl), aryl (for example, phenyl optionallysubstituted with, for example, halogen, C₁-₄alkyl, or C₁₋₄alkoxy oramino); (2) sulfonate esters, such as alkyl- or aralkylsulfonyl (forexample, methanesulfonyl); (3) amino acid esters (for example, L-valylor L-isoleucyl); (4) phosphonate esters and (5) mono-, di- ortriphosphate esters. The phosphate esters may be further esterified by,for example, a C₁₋₂₀ alcohol or reactive derivative thereof, or by a2,3-di(C₆₋₂₄)acyl glycerol.

Prodrugs and solvates of the compounds of the invention are alsocontemplated herein. A discussion of prodrugs is provided in T. Higuchiand V. Stella, Pro-drugs as Novel Delivery Systems (1987) 14 of theA.C.S. Symposium Series, and in Bioreversible Carriers in Drug Design,(1987) Edward B. Roche, ed., American Pharmaceutical Association andPergamon Press. The term “prodrug” means a compound (e.g, a drugprecursor) that is transformed in vivo to yield a compound of theinstant Formulas or a pharmaceutically acceptable salt, hydrate orsolvate of the compound. The transformation may occur by variousmechanisms (e.g., by metabolic or chemical processes), such as, forexample, through hydrolysis in blood. A discussion of the use ofprodrugs is provided by T. Higuchi and W. Stella, “Pro-drugs as NovelDelivery Systems,” Vol. 14 of the A.C.S. Symposium Series, and inBioreversible Carriers in Drug Design, ed. Edward B. Roche, AmericanPharmaceutical Association and Pergamon Press, 1987.

For example, if a compound of the instant Formulas or a pharmaceuticallyacceptable salt, hydrate or solvate of the compound contains acarboxylic acid functional group, a prodrug can comprise an ester formedby the replacement of the hydrogen atom of the acid group with a groupsuch as, for example, (C₁- C₈)alkyl, (C₂-C₁₂)alkanoyloxymethyl,1-(alkanoyloxy)ethyl having from 4 to 9 carbon atoms,1-methyl-1-(alkanoyloxy)-ethyl having from 5 to 10 carbon atoms,alkoxycarbonyloxymethyl having from 3 to 6 carbon atoms,1-(alkoxycarbonyloxy)ethyl having from 4 to 7 carbon atoms,1-methyl-1-(alkoxycarbonyloxy)ethyl having from 5 to 8 carbon atoms,N-(alkoxycarbonyl)aminomethyl having from 3 to 9 carbon atoms,1-(N-(alkoxycarbonyl)amino)ethyl having from 4 to 10 carbon atoms,3-phthalidyl, 4-crotonolactonyl, gamma-butyrolacton-4-yl,di-N,N-(C₁-C₂)alkylamino(C₂-C₃)alkyl (such as β-dimethylaminoethyl),carbamoyl-(C₁-C₂)alkyl, N,N-di(C₁-C₂)alkylcarbamoyl-(C₁-C₂)alkyl andpiperidino-, pyrrolidino- or morpholine (C₂-C₃)alkyl, and the like.

Similarly, if a compound of the instant Formulas contains an alcoholfunctional group, a prodrug can be formed by the replacement of thehydrogen atom of the alcohol group with a group such as, for example,(C₁-C₆)alkanoyloxymethyl, 1-((C₁-C₆)alkanoyloxy)ethyl,1-methyl-1((C₁-C₆)alkanoyloxy)ethyl, (C₁-C₆)alkoxycarbonyloxymethyl,N-(C₁-C₆)alkoxycarbonylaminomethyl, succinoyl, (C₁-C₆)alkanoyl,α-amino(C₁-C₄)alkanyl, arylacyl and α-aminoacyl, orα-aminoacyl-α-aminoacyl, where each α-aminoacyl group is independentlyselected from the naturally occurring L- amino acids, P(O)(OH)₂,—P(O)(O(C₁-C₆)alkyl)₂ or glycosyl (the radical resulting from theremoval of a hydroxyl group of the hemiacetal form of a carbohydrate),and the like.

If a compound of the instant Formulas incorporates an amine functionalgroup, a prodrug can be formed by the replacement of a hydrogen atom inthe amine group with a group such as, for example, R-carbonyl,RO-carbonyl, NRR′-carbonyl where R and R′ are each independently(C₁-C₁₀)alkyl, (C₃-C₇) cycloalkyl, benzyl, or R-carbonyl is a naturalα-aminoacyl or natural α-aminoacyl, —C(OH)C(O)OY¹ wherein Y¹ is H,(C₁-C₆)alkyl or benzyl, —C(OY²)Y³ wherein Y² is (C₁-C₄) alkyl and Y³ is(C₁-C₆)alkyl, carboxy(C₁-C₆)alkyl, amino(C₁-C₄)alkyl or mono-N- ordi-N,N-(C₁-C₆)alkylaminoalkyl, —C(Y⁴)Y⁵ wherein Y⁴ is H or methyl and Y⁵is mono-N- or di-N,N-(C₁-C₆)alkylamino morpholino, piperidin-1-yl orpyrrolidin-1-yl, and the like.

One or more compounds of the invention may exist in unsolvated as wellas solvated forms with pharmaceutically acceptable solvents such aswater, ethanol, and the like, and it is intended that the inventionembrace both solvated and unsolvated forms. “Solvate” means a physicalassociation of a compound of this invention with one or more solventmolecules. This physical association involves varying degrees of ionicand covalent bonding, including hydrogen bonding. In certain instancesthe solvate will be capable of isolation, for example when one or moresolvent molecules are incorporated in the crystal lattice of thecrystalline solid. “Solvate” encompasses both solution-phase andisolatable solvates. Non-limiting examples of suitable solvates includeethanolates, methanolates, and the like. “Hydrate” is a solvate whereinthe solvent molecule is H₂O.

One or more compounds of the invention may optionally be converted to asolvate. Preparation of solvates is generally known. Thus, for example,M. Caira et al, J. Pharmaceutical Sci., 93(3), 601-611 (2004) describethe preparation of the solvates of the antifungal fluconazole in ethylacetate as well as from water. Similar preparations of solvates,hemisolvate, hydrates and the like are described by E. C. van Tonder etal, AAPS PharmSciTech., 5(1), article 12 (2004); and A. L. Bingham etal, Chem. Commun., 603-604 (2001). A typical, non-limiting, processinvolves dissolving the inventive compound in desired amounts of thedesired solvent (organic or water or mixtures thereof) at a higher thanambient temperature, and cooling the solution at a rate sufficient toform crystals which are then isolated by standard methods. Analyticaltechniques such as, for example I. R. spectroscopy, show the presence ofthe solvent (or water) in the crystals as a solvate (or hydrate).

Compounds of the various Formulas, and salts, solvates, esters andprodrugs thereof, may exist in their tautomeric form (for example, as anamide or imino ether). All such tautomeric forms are contemplated hereinas part of the present invention.

The compounds of the various Formulas may contain asymmetric or chiralcenters, and, therefore, exist in different stereoisomeric forms. It isintended that all stereoisomeric forms of the compounds of the variousFormulas as well as mixtures thereof, including racemic mixtures, formpart of the present invention. In addition, the present inventionembraces all geometric and positional isomers. For example, if acompound of the various Formulas incorporates a double bond or a fusedring, both the cis- and trans-forms, as well as mixtures, are embracedwithin the scope of the invention.

Diastereomeric mixtures can be separated into their individualdiastereomers on the basis of their physical chemical differences bymethods well known to those skilled in the art, such as, for example, bychromatography and/or fractional crystallization. Enantiomers can beseparated by converting the enantiomeric mixture into a diastereomericmixture by reaction with an appropriate optically active compound (e.g.,chiral auxiliary such as a chiral alcohol or Mosher's acid chloride),separating the diastereomers and converting (e.g., hydrolyzing) theindividual diastereomers to the corresponding pure enantiomers. Also,some of the compounds of the various Formulas may be atropisomers (e.g.,substituted biaryls) and are considered as part of this invention.Enantiomers can also be separated by use of chiral HPLC column.

It is also possible that the compounds of the various Formulas may existin different tautomeric forms, and all such forms are embraced withinthe scope of the invention. Also, for example, all keto-enol andimine-enamine forms of the compounds are included in the invention.

All stereoisomers (for example, geometric isomers, optical isomers andthe like) of the present compounds (including those of the salts,solvates, esters and prodrugs of the compounds as well as the salts,solvates and esters of the prodrugs), such as those which may exist dueto asymmetric carbons on various substituents, including enantiomericforms (which may exist even in the absence of asymmetric carbons),rotameric forms, atropisomers, and diastereomeric forms, arecontemplated within the scope of this invention, as are positionalisomers (such as, for example, 4-pyridyl and 3-pyridyl). (For example,if a compound of the various Formulas incorporates a double bond or afused ring, both the cis- and trans-forms, as well as mixtures, areembraced within the scope of the invention. Also, for example, allketo-enol and imine-enamine forms of the compounds are included in theinvention.) Individual stereoisomers of the compounds of the inventionmay, for example, be substantially free of other isomers, or may beadmixed, for example, as racemates or with all other, or other selected,stereoisomers. The chiral centers of the present invention can have theS or R configuration as defined by the IUPAC 1974 Recommendations. Theuse of the terms “salt”, “solvate”, “ester”, “prodrug” and the like, isintended to equally apply to the salt, solvate, ester and prodrug ofenantiomers, stereoisomers, rotamers, tautomers, positional isomers,racemates or prodrugs of the inventive compounds.

The present invention also embraces isotopically-labelled compounds ofthe present invention which are identical to those recited herein, butfor the fact that one or more atoms are replaced by an atom having anatomic mass or mass number different from the atomic mass or mass numberusually found in nature. Examples of isotopes that can be incorporatedinto compounds of the invention include isotopes of hydrogen, carbon,nitrogen, oxygen, phosphorus, fluorine and chlorine, such as ²H, ³H,¹³C, ¹⁴C, ¹⁵N, ¹⁸N, ¹⁷O, ³¹P, ³²P, ³⁵S, ¹⁸F, and ³⁶Cl, respectively.

Certain isotopically-labelled compounds of the various Formulas (e.g.,those labelled with ³H and ¹⁴C) are useful in compound and/or substratetissue distribution assays. Tritiated (i.e., ³H) and carbon-14 (i.e.,¹⁴C) isotopes are particularly preferred for their ease of preparationand detectability. Further, substitution with heavier isotopes such asdeuterium (i.e., ²H) may afford certain therapeutic advantages resultingfrom greater metabolic stability (e.g., increased in vivo half-life orreduced dosage requirements) and hence may be preferred in somecircumstances. Isotopically labelled compounds of the various Formulascan generally be prepared by following procedures analogous to thosedisclosed in the Schemes and/or in the Examples hereinbelow, bysubstituting an appropriate isotopically labelled reagent for anon-isotopically labelled reagent.

Polymorphic forms of the compounds of the various Formulas, and of thesalts, solvates, esters and prodrugs of the compounds of the variousFormulas, are intended to be included in the present invention.

Benefits of the present invention include oral administration of anoptimal amount of a nicotinamide phosphoribosyltransferase biosynthesisinhibitor.

Benefits of the present invention include intravenous administration ofan optimal amount of a nicotinamide phosphoribosyltransferasebiosynthesis inhibitor.

Benefits of the present invention include intraperitoneal administrationof an optimal amount of a nicotinamide phosphoribosyltransferasebiosynthesis inhibitor.

Benefits of the present invention include intramural administration ofan optimal amount of a nicotinamide phosphoribosyltransferasebiosynthesis inhibitor.

Benefits of the present invention include intramuscular administrationof an optimal amount of a nicotinamide phosphoribosyltransferasebiosynthesis inhibitor.

Benefits of the present invention include subcutaneous administration ofan optimal amount of a nicotinamide phosphoribosyltransferasebiosynthesis inhibitor.

Benefits of the present invention include intra-tumor administration ofan optimal amount of a nicotinamide phosphoribosyltransferasebiosynthesis inhibitor.

Benefits of the present invention include intrathecal administration ofan optimal amount of a nicotinamide phosphoribosyltransferasebiosynthesis inhibitor.

Benefits of the present invention include subdural administration of anoptimal amount of a nicotinamide phosphoribosyltransferase biosynthesisinhibitor.

Benefits of the present invention include periorbital administration ofan optimal amount of a nicotinamide phosphoribosyltransferasebiosynthesis inhibitor.

Based on these results, the present invention has important implicationsfor the design of novel treatment strategies for patients with cancer,including leukemias and solid tumors, inflammatory diseases,osteoporosis, atherosclerosis; irritable bowel syndrome and otherconditions disclosed herein or that are known to those skilled in theart.

Description of the Preferred Embodiments

An aspect of the present invention concerns compounds disclosed herein.

An aspect of the present invention concerns compounds which are or canbe inhibitors of the formation of nicotinamidephosphoribosyltransferase.

An aspect of the present invention concerns the use of an inhibitor ofthe formation of nicotinamide phosphoribosyltransferase for thepreparation of a medicament used in the treatment, prevention,inhibition or elimination of tumors.

An aspect of the present invention concerns the use of an inhibitor ofthe formation of nicotinamide phosphoribosyltransferase for thepreparation of a medicament used in the treatment, prevention,inhibition or elimination of cancer.

An aspect of the present invention concerns the use of an inhibitor ofthe formation of nicotinamide phosphoribosyltransferase for thepreparation of a medicament used in the treatment, prevention,inhibition or elimination of cancer, where the cancer is selected fromleukemia, lymphoma, ovarian cancer, breast cancer, uterine cancer, coloncancer, cervical cancer, lung cancer, prostate cancer, skin cancer, CNScancer, bladder cancer, pancreatic cancer and Hodgkin's disease.

The present invention also describes one or more methods of synthesizingthe compounds of the present invention.

The invention also describes one or more uses of the compounds of thepresent invention.

The invention also describes one or more uses of the compounds of thepresent invention with an adjunctive agent such as use with TNF, GCSF,or other chemotherapeutic agents

The invention also describes one or more uses of the pharmaceuticalcompositions of the present invention.

An aspect of the present invention concerns the use as an inhibitor ofthe formation of nicotinamide phosphoribosyltransferase for thepreparation of a medicament used in the treatment of inflammatorydiseases.

An aspect of the present invention concerns the use as an inhibitor ofthe formation of nicotinamide phosphoribosyltransferase for thepreparation of a medicament used in the treatment of inflammatorydiseases, such as Irritable Bowel Syndrome or Inflammatory BowelDisease.

An aspect of the present invention concerns the use as an inhibitor ofthe formation of nicotinamide phosphoribosyltransferase for thepreparation of a medicament used in the treatment of disease of the bonesuch as osteoporosis.

An aspect of the present invention concerns the use as an inhibitor ofthe formation of nicotinamide phosphoribosyltransferase for thepreparation of a medicament used in the treatment of disease of thecardiovascular system, such as atherosclerosis.

An aspect of the present invention concerns the use as an inhibitor ofthe formation of nicotinamide phosphoribosyltransferase for thepreparation of a medicament used in the treatment of disease or acondition caused by an elevated level of NAMPT.

Such disease or condition is one or more selected from the groupconsisting of cancer, ovarian cancer, breast cancer, uterine cancer,colon cancer, cervical cancer, lung cancer, prostate cancer, skincancer, bladder cancer, pancreatic cancer, leukemia, lymphoma, Hodgkin'sdisease, viral infections, Human Immunodeficiency Virus, hepatitisvirus, herpes virus, herpes simplex, inflammatory disorders, irritablebowel syndrome, inflammatory bowel disease, rheumatoid arthritis,asthma, chronic obstructive pulmonary disease, osteoarthritis,osteoporosis, dermatitis, atoptic dermatitis, psoriasis, systemic lupuserythematosis, multiple sclerosis, psoriatic arthritis, ankylosingspodylitis, graft- versus-host disease, Alzheimer's disease,cerebrovascular accident, atherosclerosis, diabetes,glomerulonephiritis, metabolic syndrome, non-small cell lung cancer,small cell lung cancer, multiple myeloma, leukemias, lymphomas, squamouscell cancers, kidney cancer, uretral and bladder cancers, cancers ofhead and neck, cancers of the brain and central nervous system (CNS).

The inventive compounds can be useful in the therapy of proliferativediseases such as, but not limited to cancer, autoimmune diseases, viraldiseases, fungal diseases, neurological/neurodegenerative disorders,arthritis, inflammation, anti-proliferative (e.g., ocular retinopathy),neuronal, alopecia and cardiovascular disease.

More specifically, the compounds can be useful in the treatment of avariety of cancers, including (but not limited to) the following:carcinoma, including that of the bladder, breast, colon, kidney, liver,lung, including small cell lung cancer, non-small cell lung cancer, headand neck, esophagus, gall bladder, ovary, pancreas, stomach, cervix,thyroid, prostate, and skin, including squamous cell carcinoma;hematopoietic tumors of lymphoid lineage, including leukemia, acutelymphocytic leukemia, acute lymphoblastic leukemia, B-cell lymphoma,T-cell lymphoma, Hodgkins lymphoma, non-Hodgkins lymphoma, hairy celllymphoma, mantle cell lymphoma, myeloma, and Burkett's lymphoma;hematopoietic tumors of myeloid lineage, including acute and chronicmyelogenous leukemias, myelodysplastic syndrome and promyelocyticleukemia; tumors of mesenchymal origin, including fibrosarcoma andrhabdomyosarcoma; tumors of the central and peripheral nervous system,including astrocytoma, neuroblastoma, glioma and schwannomas; and othertumors, including melanoma, seminoma, teratocarcinoma, osteosarcoma,xenoderoma pigmentosum, keratoctanthoma, thyroid follicular cancer andKaposi's sarcoma.

The compounds of the invention may induce or inhibit apoptosis.

The compounds of the invention may also be useful in the chemopreventionof cancer. Chemoprevention is defined as inhibiting the development ofinvasive cancer by either blocking the initiating mutagenic event or byblocking the progression of pre-malignant cells that have alreadysuffered an insult or inhibiting tumor relapse.

A further aspect of the invention is a method of inhibiting a NAMPTpathway in an animal, said method comprising administering to saidanimal a pharmaceutically acceptable amount of a compound of theinvention to an animal in need thereof.

A further aspect of the invention is a pharmaceutical formulationcomprising a compound of the invention.

Another embodiment of the invention comprises a pharmaceuticalformulation of the invention, wherein the pharmaceutical formulation,upon administration to a human, results in a decrease in tumor burden.

Still another embodiment of the invention is a pharmaceuticalformulation, further comprising one or more of an antineoplastic agent,a chemotherapeutic agent, or an adjunctive chemotherapeutic agent.

The pharmaceutical formulations of the invention may further comprise atherapeutic effective amount of an adjunctive chemotherapeutic agent.

The adjunctive chemotherapeutic agent may be an agent which modifiesblood cell growth and maturation. Non-limiting examples of adjunctivechemotherapeutic agent are filgrastim, pegfilgrastim and erythropoietin.

The invention is also directed to a method of treating or preventing adisorder associated with excessive rate of growth of cells in a mammalcomprising administering to the mammal an effective amount of thepharmaceutical formulation of the invention. Non-limiting examples ofdisorder include cancer or metastasis from malignant tumors.

Another aspect of the invention is a method of inhibiting tumor cellgrowth and rate of division in a mammal with cancer, or other disorderassociated with abnormally dividing cells comprising administering tothe mammal an effective amount of the pharmaceutical formulation of thisinvention.

Another embodiment of the invention is a method of treating bone paindue to excessive growth of a tumor or metastasis to bone in a mammal inneed thereof comprising administering to the mammal an effective amountof the pharmaceutical formulation of this invention.

Still another embodiment of the invention is a method for administeringa NAMPT-inhibitor-containing compound to a mammal in need thereofcomprising administering to the mammal the pharmaceutical formulation ofthe invention. In one embodiment, the mammal is a human.

A further embodiment of the invention is a method of preparing apharmaceutical formulation comprising mixing at least onepharmaceutically acceptable compound of the present invention, and,optionally, one or more pharmaceutically acceptable excipients oradditives.

The invention is also directed to methods of synthesizing compounds ofthe present invention.

Compounds of the Invention

The invention is directed to compounds as described herein andpharmaceutically acceptable salts, solvates, esters, prodrugs or isomersthereof, and pharmaceutical compositions comprising one or morecompounds as described herein and pharmaceutically acceptable salts orisomers thereof. The invention further relates to molecules which arcuseful in inhibiting the enzyme nicotinamide phosphoribosyltransferase(NAMPT) and pharmaceutically acceptable salts, solvates, esters,prodrugs or isomers thereof.

An aspect of this invention is the provision of compounds, compositions,kits, and antidotes for the NAMPT pathway in mammals having a compoundof the Formula I:

-   wherein R is an aryl, heteroaryl, C₃-C₈ cycloalkyl, C₃-C₈    cycloalkenyl, heterocycloalkyl, arylalkyl-, (heteroaryl)alkyl-,    (C₃-C₈ cycloalkyl)alkyl-, (C₃-C8 cycloalkenyl)alkyl-,    (heterocycloalkyl)alkyl-, (aryloxy)alkyl-, (heteroaryloxy)alkyl-,    (C₃-C₈ cycloalkyloxy)alkyl-, (C₃-C₈ cycloalkenyloxy)alkyl- or    (heterocycloalkyloxy)alkyl-, wherein the heteroatom of each of said    heteroaryl and heterocycloalkyl numbers 1, 2 or 3, and is    independently selected from N, S or O, further wherein each of said    aryl, heteroaryl and heterocycloalkyl may independently be either    substituted or fused with an aryl or heteroaryl, still further    wherein any of said aryl, heteroaryl and heterocycloalkyl is either    unsubstituted or optionally independently substituted with one or    more substituents which can be the same or different and are    independently selected from the group consisting of deuterium, halo,    cyano, amino, aminoalkyl-, (amino)alkoxy-, —CONH₂, —C(O)NH(alkyl),    —C(O)N(alkyl)₂, —C(O)NH(aryl), —C(O)N(aryl)₂, —OCH₇F³⁻⁷, -alkyl,    -alkenyl, -alkynyl, -alkoxy, hydroxyl, alkyl hydroxy, hydroxyl,    alkyl hydroxy, or (alkoxyalkyl) amino-, —N(R³)—C(O)-alkyl,    —N(R³)—C(O)-aryl, -cycloalkyl, -heterocycloalkyl, -aryl, and    heteroaryl, with the proviso that no two adjacent ring heteroatoms    arc both S or both O;-   Ar is aryl, heteroaryl, heterocycloalkyl or C₃ to C₈ cycloalkyl,    with each of said aryl, heteroaryl, heterocycloalkyl and cycloalkyl    being either unsubstituted or optionally independently substituted    with 1, 2, 3 or 4 substituents which can be the same or different    and arc independently selected from the group consisting of    deuterium, halo, cyano, amino, aminoalkyl-, (amino)alkoxy-, —CONH₂,    —C(O)NH(alkyl), —C(O)N(alkyl)₂, —C(O)NH(aryl), —C(O)N(aryl)₂,    —CH_(z)F_(3−z), —OCH_(z)F_(3−z), -alkyl, -alkenyl, -alkynyl,-alkoxy,    hydroxyl, -alkyl hydroxyl, aryloxy-, (alkoxyalkyl)amino-,    —N(R³)—C(O)-alkyl, —N(R³)—C(O)-aryl, -cycloalkyl, -heterocycloalkyl,    -aryl, and -heteroaryl;-   R⁴ is cycloalkyl, —CH_(z)F_(3−z), aryl, heterocycloalkyl,    heteroaryl, alkyl, -alkenyl, -alkynyl, (aryl)alkyl-,    (heteroaryl)alkyl- or (heterocycloalkyl)alkyl-, or

-   (i) wherein each of said cycloalkyl, aryl, heterocycloalkyl,    heteroaryl and alkyl is either unsubstituted or optionally    substituted with 1, 2, 3, 4 or 5 substituents which can be the same    or different and are independently selected from the group    consisting of deuterium, halo, cyano, amino, aminoalkyl-,    (amino)alkoxy-, —CONH₂, —C(O)NH(alkyl), C(O)N(alkyl)₂,    —C(O)NH(aryl), —C(O)N(aryl)₂, —OCH₇F₃₋₇, -alkyl, alkoxy-, -alkenyl,    -alkynyl, aryloxy-, (alkoxyalkyl)amino-, -cycloalkyl,    -heterocycloalkyl, (heterocycloalkyl)alkyl-, -aryl, (aryl)alkyl-,    -heteroaryl, (heteroaryl)alkyl-, —S(O)₂-alkyl, —S(O)₂-aryl,    —S(O)₂—CF₃, —C(O)N(alkyl)₂, —C(O)alkyl, —N(R³)—C(O)-alkyl,    —N(R³)—C(O)-aryl, —S(O₂)NH₂, —S(O₂)NH(alkyl), —S(O₂)N(alkyl)₂,    —N(H)S(O₂)(alkyl), —C(O)N(H)(alkyl), and methylenedioxy, (ii)    further wherein each of said cycloalkyl, aryl, heterocycloalkyl, and    heteroaryl may optionally additionally be fused with independently    selected aryl, heteroaryl, heterocycloalkyl or cycloalkyl;-   R³ is H, alkyl or arylalkyl-;-   X is S, S(O), S(O)₂, O or C(O);-   n is 1, 2, 3 or 4;-   m is 0, 1, 2, 3 or 4;-   q is 0 or 1;-   t is 0, 1 or 2; and-   z is 0, 1 or 2;-   and pharmaceutically acceptable salts, solates, esters, prodrugs and    isomers thereof.

In the compounds of Formula I, the various moieties are independentlyselected.

The following embodiments are directed to Formula I, as applicable. Forany moieties that are not specifically defined, the previous definitionscontrol. Further, the moieties aryl, heteroaryl, and heterocycloalkyl inthese embodiments can be independently unsubstituted or optionallysubstituted or optionally fused as described earlier. Any one or more ofthe embodiments relating to Formula I below can be combined with one ormore other embodiments of Formula I.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, R is aryl, andn, m, q, t, z, Ar, X, R⁴ and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, R isheteroaryl, and n, m, q, t, z, Ar, X, R⁴ and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI where the various moieties are independently selected, Ar is aryl, andR, n, m, q, t, z, X, R⁴ and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, Ar isheteroaryl, and R, n, m, q, t, z, X, R⁴ and R³ are as defined.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, Ar, R, n, m,q, t, z, R⁴ and R³ are as defined and X is S.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, Ar, R, n, m,q, t, z, R⁴ and R³ are as defined and X is S(O).

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, Ar, R, n, m,q, t, z, R⁴ and R³ are as defined and X is S(O₂).

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, Ar, R, n, m,q, t, z, R⁴ and R³ are as defined and X is O.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, Ar, R, n, m,q, t, z, R⁴ and R³ are as defined and X is C(O).

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, Ar, R, n, m,q, t, z, R⁴ and R³ are as defined and X is C(O).

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, Ar, R, n, m,q, t, z, R⁴ and X are as defined and R³ is H.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, Ar, R, n, m,q, t, z, R⁴ and X are as defined and R³ is alkyl.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, Ar, R, n, m,q, t, z, R⁴ and X are as defined and R³ is arylalkyl.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, Ar, R, n, m,q, t, z, R³ and X are as defined and R⁴ is aryl.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, Ar, R, n, m,q, t, z, R³ and X are as defined and R⁴ is heteroaryl.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, Ar, R, n, m,q, t, z, R³ and X are as defined and R⁴ is heterocycloalkyl.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, R is aryl, R⁴is heteroaryl, and n, m, q, t, z, Ar, R³ and X are as defined.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, R is aryl, R⁴is aryl, and n, m, q, t, z, Ar, R³ and X are as defined.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, R isheteroaryl, R⁴ is heteroaryl, and n, m, q, t, z, Ar, R³ and X are asdefined.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, R isheteroaryl, R⁴ is aryl, and n, m, q, t, z, Ar, R³ and X are as defined.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, R is phenyl,R¹ is heteroaryl, and n, m, q, t, z, Ar, R³ and X are as defined.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, R is phenyl,R⁴ is aryl, and n, m, q, t, R¹, R³ z, and Ar are as defined.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, R isheteroaryl, R⁴ is phenyl, and n, m, q, t, z, Ar, R³ and X are asdefined.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, R ispyrrolopyridinyl, R⁴ is phenyl, and n, m, q, t, Ar, z, R³ and X are asdefined.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, R isoxadiazolyl, R⁴ is phenyl, and n, m, q, t, Ar, z, R³ and X are asdefined.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, R isoxadiazolyl (substituted with pyridinyl), R⁴ is phenyl, and n, m, q, t,z, Ar, R³ and X are as defined.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, R ispyrazolyl, R⁴ is phenyl, and n, m, q, t, z, Ar, R³ and X are as defined.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, R is pyrazolyl(substituted with pyridinyl), R⁴ is phenyl, and n, m, q, t, z, Ar, R³and X are as defined.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties arc independently selected, R isimidazolyl, R⁴ is phenyl, and n, m, q, t, Ar, z, R³ and X are asdefined.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, R istriazolopyridinyl, R⁴ is phenyl, and n, m, q, t, z, Ar, R³ and X are asdefined.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, R isnaphthyridinyl, R⁴ is phenyl, and n, m, q, t, z, Ar, R³ and X are asdefined.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, R istetrazolopyridinyl, R⁴ is phenyl, and n, m, q, t, z, Ar, R³ and X are asdefined.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, R isisoquinolinyl, R⁴ is phenyl, and n, m, q, t, Ar, R³ z, and X are asdefined.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, R isquinolinyl, R⁴ is phenyl, and n, m, q, t, Ar, z, R³ and X are asdefined.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, R isimidazopyrazinyl, R⁴ is phenyl, and n, m, q, t, z, Ar, R³ and X are asdefined.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, R isquinazolinyl, R⁴ is phenyl, and n, m, q, t, z, Ar, R³ and X are asdefined.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, R isbenzothiazolyl, R⁴ is phenyl, and n, m, q, t, z, Ar, R³ and X are asdefined.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, R isthienopyridinyl, R⁴ is phenyl, and n, m, q, t, z, Ar, R³ and X are asdefined.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, R ispyrrolopyridinyl, R⁴ is thiophenyl, and n, m, q, z, t, Ar, R³ and X areas defined.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, R isoxadiazolyl, R⁴ is naphthalinyl, and n, m, q, t, z, Ar, R³ and X are asdefined.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, R isoxadiazolyl (substituted with pyridinyl), R⁴ is quinolinyl, and n, m, q,z, t, Ar, R³ and X are as defined.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, R ispyrazolyl, R⁴ is isoquinolinyl, and n, m, q, t, z, Ar, R³ and X are asdefined.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, R is pyrazolyl(substituted with pyridinyl), R⁴ is benzodioxinyl, and n, m, q, t, z,Ar, R³ and X are as defined.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, R isimidazolyl, R⁴ is phenoxathiinyl, and n, m, q, t, z, Ar, R³ and X are asdefined.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, R ispyrrolopyridinyl, R⁴ is phenyl, Ar is phenyl, and n, m, q, t, z, R³ andX are as defined.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, R isoxadiazolyl, R⁴ is phenyl, Ar is phenyl, and n, m, q, t, z, R³ and X areas defined.

An embodiment of the invention is the provision of a compound of FormulaId, where the various moieties are independently selected, R isoxadiazolyl (substituted with pyridinyl), R⁴ is phenyl, Ar is phenyl,and n, m, z, q, t, R³ and X are as defined.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, R ispyrazolyl, R⁴ is phenyl, Ar is phenyl, and n, m, q, t, z, R³ and X areas defined.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, R is pyrazolyl(substituted with pyridinyl), R⁴ is phenyl, Ar is phenyl, and n, m, q,z, t, R³ and X are as defined.

An embodiment of the invention is the provision of a compound, where thevarious moieties are independently selected, R is imidazolyl, R⁴ isphenyl, Ar is phenyl, and n, m, q, t, z, R³ and X are as defined.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, R istriazolopyridinyl, R⁴ is phenyl, Ar is phenyl, and n, m, q, t, z, R³ andX are as defined.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, R isnaphthyridinyl, R⁴ is phenyl, Ar is phenyl, and n, m, q, t, z, R³ and Xare as defined.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, R istetrazolopyridinyl, R⁴ is phenyl, Ar is phenyl, and n, m, q, t, z, R³and X are as defined.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, R isisoquinolinyl, R⁴ is phenyl, Ar is phenyl, and n, m, q, t, z, R³ and Xare as defined.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, R isquinolinyl, R⁴ is phenyl, Ar is phenyl, and n, m, q, t, z, R³ and X areas defined.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, R isimidazopyrazinyl, R⁴ is phenyl, Ar is phenyl, and n, m, q, t, z, R³ andX are as defined.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, R isquinazolinyl, R⁴ is phenyl, Ar is phenyl, and n, m, q, t, z, R³ and Xare as defined.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, R isbenzothiazolyl, R⁴ is phenyl, Ar is phenyl, and n, m, q, t, z, R³ and Xarc as defined.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, R isthienopyridinyl, R⁴ is phenyl, Ar is phenyl, and n, m, q, t, z, R³ and Xarc as defined.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, R ispyrrolopyridinyl, R⁴ is phenyl, Ar is phenyl, n is 1, m is 1, q is 0, tis 0, z is 0, R³ and X are as defined.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, R isoxadiazolyl, R⁴ is phenyl, Ar is phenyl, n is 1, m is 1, q is 0, t is 0,z is 0, R³ and X are as defined.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, R isoxadiazolyl (substituted with pyridinyl), R⁴ is phenyl, Ar is phenyl, nis 1, m is 1, q is 0, t is 0, z is 0, R³ and X are as defined.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, R ispyrazolyl, R⁴ is phenyl, Ar is phenyl, n is 1, m is 1, q is 0, t is 0, zis 0, R³ and X are as defined.

An embodiment of the invention is the provision of a compound of FormulaI where the various moieties are independently selected, R is pyrazolyl(substituted with pyridinyl), R⁴ is phenyl, Ar is phenyl, n is 1, m is1, q is 0, t is 0, z is 0, R³ and X are as defined.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, R isimidazolyl, R⁴ is phenyl, Ar is phenyl, n is 1, m is 1, q is 0, t is 0,z is 0, R³ and X are as defined.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, R istriazolopyridinyl, R⁴ is phenyl, Ar is phenyl, n is 1, m is 1, q is 0, tis 0, z is 0, R³ and X are as defined.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, R isnaphthyridinyl, R⁴ is phenyl, Ar is phenyl, n is 1, m is 1, q is 0, t is0, z is 0, R³ and X are as defined.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, R istetrazolopyridinyl, R⁴ is phenyl, Ar is phenyl, n is 1, m is 1, q is 0,t is 0, z is 0, R³ and X are as defined.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, R isisoquinolinyl, R⁴ is phenyl, Ar is phenyl, n is 1, m is 1, q is 0, t is0, z is 0, R³ and X are as defined.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, R isquinolinyl, R⁴ is phenyl, Ar is phenyl, n is 1, m is 1, q is 0, t is 0,z is 0, R³ and X are as defined.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, R isimidazopyrazinyl, R⁴ is phenyl, Ar is phenyl, n is 1, m is 1, q is 0, tis 0, z is 0, R³ and X are as defined.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, R isquinazofinyl, R⁴ is phenyl, Ar is phenyl, n is 1, m is 1, q is 0, t is0, z is 0, R³ and X are as defined.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, R isbenzothiazolyl, R⁴ is phenyl, Ar is phenyl, n is 1, m is 1, q is 0, t is0, z is 0, R³ and X are as defined.

An embodiment of the invention is the provision of a compound of FormulaI, where the various moieties are independently selected, R isthienopyridinyl, R⁴ is phenyl, Ar is phenyl, n is 1, m is 1, q is 0, tis 0, z is 0, R³ and X are as defined.

Another aspect of the invention arc the compounds of Formula I, whereq=0, m=0, t=0, Ar=A, X=Q and R4 is

and the formula is now Formula IB

wherein

-   R and R³ arc as defined in Formula I;-   R¹ and R² are the same or they are different, and are independently    selected from H, a straight or branched C₁ to C₇ alkyl, straight or    branched C₁ to C₇ alkoxy, straight or branched C₁ to C₄    hydroxyalkyl, aryl, heteroaryl, heterocycloalkyl and cycloalkyl, and    wherein heteroatoms of said heteroaryl and heterocycloalkyl are    independently selected from one or more N, O and S, with the proviso    that no two adjacent ring heteroatoms are both S or both O, further    wherein R¹ and R² can be either unsubstituted or optionally    independently substituted with one or more substituents which can be    the same or different and are independently selected from the group    consisting of deuterium, halo, cyano, amino, aminoalkyl-,    (amino)alkoxy-, —CONH₂, —C(O)NH(alkyl), —C(O)N(alkyl)₂,    —C(O)NH(aryl), —C(O)N(aryl)₂, —CH_(z)F_(3−z), —OCH_(z)F_(3−z),    -alkyl, -alkenyl, -alkynyl, hydroxyalkyl-, -alkoxy, hydroxyl, alkyl    hydroxy, carboxy, (alkoxyalkyl) amino-, -alkylamine, aminocarbonyl-,    —CHO, —N(R³)—C(O)-alkyl, —N(R³)—C(O)-aryl, -cycloalkyl,    -heterocycloalkyl, -aryl, and heteroaryl;-   A is aryl, heteroaryl, heterocycloalkyl or C₃ to C₈ cycloalkyl, with    each of said aryl, heteroaryl, heterocycloalkyl and cycloalkyl being    either unsubstituted or optionally independently substituted with 1,    2, 3 or 4 substituents which can be the same or different and are    independently selected from the group consisting of deuterium, halo,    cyano, amino, aminoalkyl-, (amino)alkoxy-, —CONH₂, —C(O)NH(alkyl),    —C(O)N(alkyl)₂, —C(O)NH(aryl), —C(O)N(aryl)₂, —OCH_(z)F_(3−z),    -alkyl, -alkenyl, -alkynyl,-alkoxy, hydroxyl, -alkyl hydroxyl,    aryloxy-, (alkoxyalkyl)amino-, —N(R³)—C(O)-alkyl, —N(R³)—C(O)-aryl,    -cycloalkyl, -heterocycloalkyl, -aryl, and -heteroaryl;-   Q is C(O), S(O), S(O)₂, —N(H)—C(O)—, —S(O₂)—NH—, or —N(H)—S(O₂)—;-   n is 0, 1, 2, 3 or 4; and-   z is 0, 1 or 2;-   and pharmaceutically acceptable salts, solvates, esters, prodrugs or    isomers thereof.

Another embodiment of Formula IB are compounds of Formula IC

wherein

-   R, A, Q, R³, z and n are as defined in Formula IB, and-   R¹ and R² are joined together to form, along with the N they are    shown attached to in the formula, a C₃-C₈ heterocycloalkyl, a C₃-C₈    heterocycloalkenyl, a fused bicyclic heterocycloalkyl, a fused    tricyclic heterocycloalkyl, spiroheterocycloalkyl, or a    heterospiroheterocycloalkyl, wherein each of said heterocycloalkyl,    heterocycloalkenyl, spiroheterocycloalkyl, and    heterospiroheterocycloalkyl can optionally contain one or more    heteroatoms in addition to the N atom they are shown attached to in    the formula, said heteroatoms being selected from N, S and O, with    the proviso that no two adjacent ring heteroatoms are both S or both    O, further wherein each of said heterocycloalkyl and    heterocycloalkenyl can be either unsubstituted or optionally    independently substituted with one or more substituents which can be    the same or different and arc independently selected from the group    consisting of deuterium, halo, cyano, amino, aminoalkyl-,    (amino)alkoxy-, —CONH₂, —C(O)NH(alkyl), —C(O)N(alkyl)₂,    —C(O)NH(aryl), —C(O)N(aryl)₂, —CH_(z)F_(3−z), —OCH_(z)F_(3−z),    -alkyl, -alkenyl, -alkynyl, hydroxyalkyl, -alkoxy, hydroxyl, -alkyl    hydroxy, carboxy, (alkoxyalkyl) amino-, -alkylamine, aminocarbonyl-,    —CHO, —N(R³)—C(O)-alkyl, —N(R³)—C(O)-aryl, -cycloalkyl,    -heterocycloalkyl, -aryl, and heteroaryl;-   and pharmaceutically acceptable salts thereof.

In the compounds of Formulas IB and C the various moieties areindependently selected.

The following embodiments are directed to Formula IB and C, asapplicable. For any moieties that are not specifically defined, theprevious definitions control. Further, the moieties aryl, heteroaryl,heterocycloalkyl, cycloalkyl, cycloalkenyl and heterocycloalkenyl inthese embodiments can be independently unsubstituted or optionallysubstituted or optionally fused as described earlier. Any one or more ofthe embodiments relating to Formula IB and IC below can be combined withone or more other embodiments for Forumula IB and IC.

An embodiment of the invention is the provision of a compound ofFormulas IB and IC, where the various moieties are independentlyselected, R is aryl, and n, A, Q and R¹ and R² are as defined.

Another embodiment of the invention is the provision of a compound ofFormulas IB and IC where the various moieties are independentlyselected, R is heteroaryl, and n, A, Q and R¹ and R² are as defined.

Another embodiment of the invention is the provision of a compound ofFormulas IB and IC, the various moieties are independently selected, Ris C₃-C₈ cycloalkyl, and n, A, Q and R1 and R² are as defined.

Another embodiment of the invention is the provision of a compound ofFormula IB and IC, where the various moieties are independentlyselected, R is C₃-C₈ cycloalkenyl, and n, A, Q and R¹ and R² are asdefined.

Another embodiment of the invention is the provision of a compound ofFormula IB and IC, where the various moieties are independentlyselected, R is heterocycloalkyl, and n, A, Q and R¹ and R² are asdefined.

Another embodiment of the invention is the provision of a compound ofFormula IB and IC, where the various moieties are independentlyselected, R is arylalkyl, and n, A, Q and R¹ and R² are as defined.

Another embodiment of the invention is the provision of a compound ofFormula IB and IC, where the various moieties are independentlyselected, R is (heteroaryl)alkyl, and n, A, Q and R¹ and R²are asdefined.

Another embodiment of the invention is the provision of a compound ofFormula IB and IC where the various moieties are independently selected,R is (C₃-C₈ cycloalkyl)alkyl, and n, A, Q and R¹ and R² are as defined.

Another embodiment of the invention is the provision of a compound ofFormula IB and IC, where the various moieties are independentlyselected, R is (C₃-C₈ cycloalkenyl)alkyl, and n, A, Q and R¹ and R² areas defined.

Another embodiment of the invention is the provision of a compound ofFormula IB and IC, where the various moieties are independentlyselected, R is (heterocycloalkyl)alkyl, and n, A, Q and R¹ and R² are asdefined.

Another embodiment of the invention is the provision of a compound ofFormula IB and IC, where the various moieties are independentlyselected, R is (aryloxy)alkyl, and n, A, Q and R¹ and R² are as defined.

Another embodiment of the invention is the provision of a compound ofFormula IB and IC, where the various moieties are independentlyselected, R is (heteroaryloxy)alkyl, and n, A, Q and R¹ and R² are asdefined.

Another embodiment of the invention is the provision of a compound ofFormula IB and IC, where the various moieties are independentlyselected, R is (C₃-C₈ cycloalkyloxy)alkyl, and n, A, Q and R¹ and R² areas defined.

Another embodiment of the invention is the provision of a compound ofFormula IB, where the various moieties are independently selected, R is(C₃-C₈ cycloalkenyloxy)alkyl, and n, A, Q and R¹ and R² are as defined.

Another embodiment of the invention is the provision of a compound ofFormula IB and IC, where the various moieties are independentlyselected, R is (heterocycloalkyloxy)alkyl, and n, A, Q and R¹ and R² areas defined.

Another embodiment of the invention is the provision of a compound ofFormula IB and IC, where the various moieties are independentlyselected, R, n, Q

and R1 and R²are as defined and A is aryl.

Another embodiment of the invention is the provision of a compound ofFormula IB and IC, where the various moieties are independentlyselected, R, n, Q and G are as defined and A is heteroaryl.

Another embodiment of the invention is the provision of a compound ofFormula IB and IC, where the various moieties are independentlyselected, R, n, Q and R1 and R²are as defined and A is heterocycloalkyl.

Another embodiment of the invention is the provision of a compound ofFormula IB and IC, where the various moieties are independentlyselected, R, n, Q and R1 and R²are as defined and A is C₃-C₈ cycloalkyl.

Another embodiment of the invention is the provision of a compound ofFormula IB and IC, where the various moieties are independentlyselected, R, A, Q and R1 and R² are as defined and n is 0.

Another embodiment of the invention is the provision of a compound ofFormula IB and IC, where the various moieties are independentlyselected, R, A, Q and R1 and R²are as defined and n is 1.

Another embodiment of the invention is the provision of a compound ofFormula IB and IC, where the various moieties are independentlyselected, R, A, Q and R1 and R²are as defined and n is 2.

Another embodiment of the invention is the provision of a compound ofFormula IB and IC, where the various moieties are independentlyselected, R, A, Q and R1 and R²are as defined and n is 3.

Another embodiment of the invention is the provision of a compound ofFormula IB and IC, where the various moieties are independentlyselected, R, A, Q and R1 and R²are as defined and n is 4.

Another embodiment of the invention is the provision of a compound ofFormula IB, where the various moieties are independently selected, R, A,n and R1 and R²are as defined and Q is C(O).

Another embodiment of the invention is the provision of a compound ofFormula IB and IC, where the various moieties are independentlyselected, R, A, n and R¹ and R²are as defined and Q is S(O).

Another embodiment of the invention is the provision of a compound ofFormula IB and IC, where the various moieties are independentlyselected, R, A, n and R¹ and R²are as defined and Q is S(O₂).

Another embodiment of the invention is the provision of a compound ofFormula IB and IC, where the various moieties are independentlyselected, R, A, n and R¹ and R²are as defined and Q is —N(H)—S(O₂)—.

Another embodiment of the invention is the provision of a compound ofFormula IB and IC, where the various moieties are independentlyselected, R, A, n and R¹ and R²are as defined and Q is —S(O₂)—N(H)—.

Another embodiment of the invention is the provision of a compound ofFormula IB and IC, where the various moieties are independentlyselected, R, A, n and R¹ and R²are as defined and Q is —N(H)—C(O)—.

An embodiment of the invention is the provision of a compound of FormulaIB and IC, where the various moieties are independently selected, R isphenyl, and n, A, Q and R¹ and R² are as defined.

An embodiment of the invention is the provision of a compound of FormulaIB and IC, where the various moieties are independently selected, R isnaphthyl, and n, A, Q and R¹ and R² are as defined.

An embodiment of the invention is the provision of a compound of FormulaIB and IC, where the various moieties are independently selected, R ispyridyl, and n, A, Q and R¹ and R² are as defined.

An embodiment of the invention is the provision of a compound, whereFormulas IB and IC the various moieties are independently selected, R isa pyrrolopyridinyl group, and n, A, Q and R¹ and R² are as defined.

An embodiment of the invention is the provision of a compound of FormulaIB and IC, where the various moieties are independently selected, R is athienopyridinyl group, and n, A, Q and R1 and R²are as defined.

An embodiment of the invention is the provision of a compound of FormulaIB and IC, where the various moieties are independently selected, R isan indazolyl group, and n, A, Q and R¹ and R² are as defined.

An embodiment of the invention is the provision of a compound of FormulaIB and IC, where the various moieties are independently selected, R is apyrazolopyridinyl group, and n, A, Q and R1 and R² are as defined.

An embodiment of the invention is the provision of a compound of FormulaIB and IC, where the various moieties are independently selected, R isan imidazopyridinyl group, and n, A, Q and R¹ and R² are as defined.

An embodiment of the invention is the provision of a compound of FormulaIB and IC, where the various moieties are independently selected, R isan imidazopyrazolyl group, and n, A, Q and R¹ and R² are as defined.

An embodiment of the invention is the provision of a compound of FormulaIB and IC, where the various moieties are independently selected, R is atetrazolopyridinyl group, and n, A, Q and R¹ and R² are as defined.

An embodiment of the invention is the provision of a compound of FormulaIB and IC, where the various moieties are independently selected, R is anaphthyridinyl group, and n, A, Q and R¹ and R² are as defined.

An embodiment of the invention is the provision of a compound of FormulaIB and IC, where the various moieties are independently selected, R is abenzodiazolyl group, and n, A, Q and R¹ and R² are as defined.

An embodiment of the invention is the provision of a compound of FormulaIB and IC, where the various moieties are independently selected, R is abenzothiazolyl group, and n, A, Q and R1 and R² are as defined.

An embodiment of the invention is the provision of a compound of FormulaIB and IC, where the various moieties are independently selected, R is afuropyridinyl group, and n, A, Q and R1 and R² are as defined.

An embodiment of the invention is the provision of a compound of FormulaIB and I C, where the various moieties are independently selected, R isa (pyridinyloxy)methyl group, and n, A, Q and R¹ and R² are as defined.

Another embodiment of the invention is the provision of a compound ofFormula IB and IC, where the various moieties are independentlyselected, R is (pyridinyl)alkyl, and n, A, Q and R¹ and R² are asdefined.

Another embodiment of the invention is the provision of a compound ofFormula IB and IC, where the various moieties are independentlyselected, R is (pyridinyl)ethyl, and n, A, Q and R¹ and R² are asdefined.

Another embodiment of the invention is the provision of a compound ofFormula IB and IC, where the various moieties are independentlyselected, R is (pyrrolopyridinyl)methyl, and n, A, Q and R1 and R² areas defined.

Another embodiment of the invention is the provision of a compound ofFormula IB and IC, where the various moieties are independentlyselected, R, n, Q and RI and R² are as defined and A is phenyl.

Another embodiment of the invention is the provision of a compound ofFormula IB and IC, where the various moieties are independentlyselected, R, n, Q and R1 and R² are as defined and A is piperidinyl.

Another embodiment of the invention is the provision of a compound ofFormula IB and IC, where the various moieties are independentlyselected, R, A, n, R², and Q are as defined, and R¹ is H.

Another embodiment of the invention is the provision of a compound ofFormula IB, where the various moieties are independently selected, R, A,n, R¹, and Q are as defined, and —R² is piperidinyl.

Another embodiment of the invention is the provision of a compound ofFormula IB, where the various moieties are independently selected, R, A,n, R¹, and Q are as defined, and —R² is quinolinyl.

Another embodiment of the invention is the provision of a compound ofFormula IB, where the various moieties are independently selected, R, A,n, R¹, and Q are as defined, R1 is H and —R² is morpholinyl.

Another embodiment of the invention is the provision of a compound ofFormula IB, where the various moieties are independently selected, R, A,n, R¹, and Q are as defined, R¹ is H and —R² is piperidinyl.

Another embodiment of the invention is the provision of a compound ofFormula IB, where the various moieties are independently selected, R, A,n, R¹, and Q are as defined, R1 is H and —R² is quinolinyl.

Another embodiment of the invention is the provision of a compound ofFormula IB, where the various moieties are independently selected, R, A,n, R¹, and Q are as defined, and —R² is morpholinyl.

Another embodiment of the invention is the provision of a compound ofFormula IB and IC, where the various moieties are independentlyselected, n, R¹, R², and Q are as defined, both A and R are aryl.

Another embodiment of the invention is the provision of a compound ofFormula IB and IC, where the various moieties are independentlyselected, n, R¹, R², and Q are as defined, both A and R are heteroaryl.

Another embodiment of the invention is the provision of a compound ofFormula IB and IC, where the various moieties are independentlyselected, n, R¹, R², and Q are as defined, R is heteroaryl and A isaryl.

Another embodiment of the invention is the provision of a compound ofFormula IB and IC, where the various moieties are independentlyselected, n, R¹, R², and Q are as defined, R is (heteroaryl)alkyl and Ais aryl.

Another embodiment of the invention is the provision of a compound ofFormula IB and IC, where the various moieties are independentlyselected, n, R¹, R², and Q are as defined, R is (heteroaryloxy)alkyl andA is aryl.

Another embodiment of the invention is the provision of a compound ofFormula IB and IC, where the various moieties are independentlyselected, n, R¹, R², and Q are as defined, R is aryl and A isheteroaryl.

Another embodiment of the invention is the provision of a compound ofFormula IB and IC, where the various moieties are independentlyselected, n, R¹, R² are as defined, both A and R are aryl and Q isS(O₂).

Another embodiment of the invention is the provision of a compound ofFormula IB and IC, where the various moieties are independentlyselected, n, R¹, R² are as defined, both A and R are heteroaryl and Q isS(O₂).

Another embodiment of the invention is the provision of a compound ofFormula IB and IC, where the various moieties are independentlyselected, n, R¹, R² are as defined, A is aryl, R is heteroaryl and Q isS(O₂).

Another embodiment of the invention is the provision of a compound ofFormula IB and IC, where the various moieties are independentlyselected, n, R¹, R² are as defined, A is aryl, R is (heteroaryl)alkyland Q is S(O₂).

Another embodiment of the invention is the provision of a compound ofFormula IB and IC, where the various moieties are independentlyselected, n, R¹, R² are as defined, A is aryl, R is (heteroaryloxy)alkyland Q is S(O₂).

Another aspect of the invention is compounds derived from Formula Iwhere q=0, m=0 and t=0, whereby the formula becomes Formula II orpharmaceutically acceptable salts thereof:

wherein:

-   R is heteroaryl comprising 1, 2, 3 or 4 heteroatom(s) independently    selected from N, S or O, wherein said heteroaryl may be substituted    by one or more substituents selected from the group consisting of    amino, oxo, and halo; and wherein said heteroaryl can comprise one    or more N-oxide(s) formed with a N atom member of said heteroaryl;-   Ar is aryl or heteroaryl comprising 1, 2, 3 or 4 heteroatom(s)    independently selected from N, S or O;-   X is S(O)₂ or S═O;-   R¹ is —NHR⁴ and R⁴ is cycloalkyl, heterocycloalkyl, aryl or    heteroaryl;    -   cycloalkyl;    -   aryl;    -   heterocycloalkyl; or    -   heteroaryl; wherein:    -   each of said cycloalkyl, aryl, or heteroaryl is unsubstituted or        substituted with 1, 2, 3, 4 or 5 substituents which can be the        same or different and are independently selected from the group        consisting of:        -   deuterium, halo, hydroxy, hydroxyalkyl, cyano,            —(CH₂)_(m)NR^(a)R^(b), oxo, alkyl, cyanoalkyl, haloalkyl,            alkoxy, haloalkoxy, alkoxyalkyl-, alkenyl, alkynyl,            alkynylalkoxy, —CONH₂, —S-alkyl, —C(O)NH(alkyl),            —C(O)N(alkyl)₂, —C(O)NH(cycloalkyl), —C(O)NH(aryl),            —C(O)N(aryl)₂, arylalkyl-, arylalkoxy-, aryloxy-,            cycloalkyl, heterocycloalkyl, aryl,            (heterocycloalkyl)alkyl-, (heterocycloalkyl)alkoxy-,            —C(O)heterocycloalkyl, heteroaryl, (heteroaryl)alkyl-,            —S(O)₂-alkyl, —S(O)₂-aryl, —S(O)₂—CH_(z)F_(3−z), —C(O)alkyl,            —N(R⁵)—C(O)-alkyl, —N(R⁵)—C(O)-aryl, —S(O₂)NH₂,            —S(O₂)NH(alkyl), —S(O₂)N(alkyl)₂, —N(H)(SO₂)(alkyl), and            methylenedioxy, wherein each of said cycloalkyl,            heterocycloalkyl, aryl or heteroaryl may be substituted by            one or more halo, cyano, alkyl or alkoxy and;    -   each of said cycloalkyl, heterocycloalkyl, aryl, or heteroaryl        may optionally additionally be fused with independently selected        aryl, heteroaryl, heterocycloalkyl or cycloalkyl to from a        bicyclic or tricyclic group that may be substituted by one or        more halo, cyano, alkyl or alkoxy;-   R² and R³ can be independently selected from the group consisting of    H and deuterium;-   R⁵ is H, alkyl or arylalkyl-;-   R^(a) and R^(b) are independently selected from the group consisting    of H, alkyl, alkoxy, alkoxyalkyl and haloalkyl;-   m is 0, 1, 2, 3, 4, 5 or 6; and-   n is 0 or 1;

An embodiment of Formula II of this invention is the provision ofcompounds compositions, kits and andtidotes for the NAMPT pathway inmammals where X is S(O)₂ and n=1, the formula now becoming the FormulaII A:

wherein:

-   R is heteroaryl comprising 1, 2, 3 or 4 heteroatom(s) independently    selected from N, S or O, wherein said heteroaryl may be substituted    by one or more substituents selected from the group consisting of    amino, oxo, and halo ; and wherein said heteroaryl can comprise one    or more N-oxide(s) formed with a N atom member of said heteroaryl;-   Ar is aryl or 5 or 6 membered heteroaryl comprising 1, 2, 3 or 4    heteroatom(s) independently selected from N, S or O;-   R¹ is —NHR⁴ where R⁴ is cycloalkyl, heterocycloalkyl, aryl or    heteroaryl;    -   cycloalkyl;    -   aryl; or    -   heteroaryl; wherein:    -   each of said cycloalkyl, aryl, or heteroaryl is unsubstituted or        substituted with 1, 2, 3, 4 or 5 substituents which can be the        same or different and are independently selected from the group        consisting of:        -   deuterium, halo, hydroxy, hydroxyalkyl, cyano,            —(CH₂)_(m)NR^(a)R^(b), oxo, alkyl, cyanoalkyl, haloalkyl,            alkoxy, haloalkoxy, alkoxyalkyl-, alkenyl, alkynyl,            alkynylalkoxy, —CONH₂, —S-alkyl, —C(O)NH(alkyl),            —C(O)N(alkyl)₂, —C(O)NH(cycloalkyl), —C(O)NH(aryl),            —C(O)N(aryl)₂, arylalkyl-, arylalkoxy-, aryloxy-,            cycloalkyl, heterocycloalkyl, aryl,            (heterocycloalkyl)alkyl-, (heterocycloalkyl)alkoxy-,            —C(O)heterocycloalkyl, heteroaryl, (heteroaryl)alkyl-,            —S(O)₂-alkyl, —S(O)₂-aryl, —S(O)₂—CH_(z)F_(3−z), —C(O)alkyl,            —N(R⁵)—C(O)-alkyl, —N(R⁵)—C(O)-aryl, —S(O₂)NH₂,            —S(O₂)NH(alkyl), —S(O₂)N(alkyl)₂, —N(H)(SO₂)(alkyl), and            methylenedioxy, wherein each of said cycloalkyl,            heterocycloalkyl, aryl or heteroaryl may be substituted by            one or more halo, cyano, alkyl or alkoxy and;    -   each of said cycloalkyl, heterocycloalkyl, aryl, or heteroaryl        may optionally additionally be fused with independently selected        aryl, heteroaryl, heterocycloalkyl or cycloalkyl to from a        bicyclic or tricyclic group that may be substituted by one or        more halo, cyano, alkyl or alkoxy;-   R² and R³ can be independently selected from the group consisting of    H and deuterium;-   R⁵ is H, alkyl or arylalkyl-;-   R^(a) and R^(b) are independently selected from the group consisting    of H, alkyl, alkoxy, alkoxyalkyl and haloalkyl; and-   m is 0, 1, 2, 3, 4, 5 or 6.

In the compounds of Formulas II, and IIA, the various moieties areindependently selected.

The following embodiments are directed to Formulas II, and IIA asapplicable. For any moieties that are not specifically defined, theprevious definitions control. Further, the moieties aryl, heteroaryl,heterocycloalkyl, cycloalkyl, cycloalkenyl and heterocycloalkenyl inthese embodiments can be independently unsubstituted or optionallysubstituted or optionally fused as described earlier. Any one or more ofthe embodiments relating to Formula II or IIA below can be combined withone or more other embodiments for Formula II or IIA.

An embodiment of the invention is the provision of a compound of FormulaII or IIA where the various moieties are independently selected and Aris aryl.

An embodiment of the invention is the provision of a compound of FormulaII or IIA where the various moieties are independently selected and Aris phenyl.

Another embodiment of the invention is the provision of a compound ofFormula II or IIA where the various moieties are independly selected andAr has the formula of:

Another embodiment of the invention is the provision of a compound ofFormula II or IIA where the various moieties are independly selected andAr is 5 or 6 membered heteroaryl.

Another embodiment of the invention is the provision of a compound ofFormula II or IIA where the various moieties are independly selected andAr is pyridine.

Another embodiment of the invention is the provision of a compound ofFormula II or IIA where the various moieties are independly selected andR is a bicyclic heteroaryl.

Another embodiment of the invention is the provision of a compound ofFormula II or IIA where the various moieties are independly selected andR is a 9 to 10 membered bicyclic heteroaryl containing 1, 2, 3, or 4heteroatoms independently selected from N, S or O.

Another embodiment of the invention is the provision of a compound ofFormula II or IIA where the various moieties arc independly selected andR is selected from benzothiazole, dihydronaphthyridine,dihydropyridopyrimidine, dihydropyrrolopyridine, furopyridine,imidazopyrazine, imidazopyrazole imidazopyridine, imidazopyrimidine,indazole, indole, isoquinoline, naphthyridine, pyrazolopyridine,pyrrolopyridine, tetrazolopyridine, tetrahydroimidazopyridine,tetrahydropyrazolopyridine, thiazolopyridine and thienopyridine.

Another embodiment of the invention is the provision of a compound ofFormula II or IIA where the various moieties are independently selectedand R is selected from 1H-pyrazolo[3,4-b]pyridine;1,4,6,7-Tetrahydro-pyrazolo[4,3-c]pyridine;7,8-Dihydro-5H-pyrido[4,3-d]pyrimidine;5,7-Dihydro-pyrrolo[3,4-b]pyridine; 7,8-Dihydro-5H-[1,6]naphthyridine;1,4,6,7-Tetrahydro-imidazo[4,5-c]pyridine;1,8a-dihydroimidazo[1,2-a]pyridine; thieno[3,2-c]pyridine;1H-imidazo[1,2-b]pyrazole; 1H-pyrazolo[3,4-b]pyridine;furo[2,3-c]pyridine; 1H-pyrazolo[3,4-b]pyridine;1H-pyrrolo[3,2-c]pyridine; thieno[2,3-b]pyridine;imidazo[1,2-a]pyrimidine; furo[2,3-c]pyridine; isoquinoline;1H-indazole; imidazo[1,2-a]pyridine; thieno[2,3-c]pyridine;furo[2,3-c]pyridine; 1H-pyrrolo[2,3-c]pyridine; imidazo[1,2-a]pyrazine;1,3-benzothiazole; benzo[d]thiazole; 1H-pyrrolo[2,3-b]pyridine;[1,3]thiazolo[5,4-c]pyridine; [1,2,3,4]tetrazolo[1,5-a]pyridine;1,5-naphthyridine; 1H-indole; 1H-imidazo[4,5-c]pyridine; and1,6-naphthyridine.

Another embodiment of the invention is the provision of compounds ofFormula II or IIA wherein R is selected from the group consisting of:

Another embodiment of the invention is the provision of a compound ofFormula II or IIA where the various moieties are independly selected, Aris aryl and R is a 9 to 10 membered bicyclic heteroaryl containing 1, 2,3, or 4 heteroatoms independently selected from N, S or O.

Another embodiment of the invention is the provision of a compound ofFormula II or IIA where the various moieties are independly selected, Aris phenyl and R is a 9 to 10 membered bicyclic heteroaryl containing 1,2, 3, or 4 heteroatoms independently selected from N, S or O.

Another embodiment of the invention is the provision of a compound ofFormula II or IIA where the various moieties are independly selected, Aris phenyl and R is selected from benzothiazole, dihydronaphthyridine,dihydropyridopyrimidine, dihydropyrrolopyridine, furopyridine,imidazopyrazine, imidazopyrazole imidazopyridine, imidazopyrimidine,indazole, indole, isoquinoline, naphthyridine, pyrazolopyridine,pyrrolopyridine, tetrazolopyridine, tetrahydroimidazopyridine,tetrahydropyrazolopyridine, thiazolopyridine and thienopyridine.

Another embodiment of the invention is the provision of a compound ofFormula II or IIA where the various moieties are independly selected andAr is 5 or 6 membered heteroaryl and R is a 9 to 10 membered bicyclicheteroaryl containing 1, 2, 3, or 4 heteroatoms independently selectedfrom N, S or O.

Another embodiment of the invention is the provision of a compound ofFormula II or IIA where the various moieties are independly selected, Aris pyridine and R is a 9 to 10 membered bicyclic heteroaryl containing1, 2, 3, or 4 heteroatoms independently selected from N, S or O.

Another embodiment of the invention is the provision of a compound ofFormula II or IIA where the various moieties are independently selectedand R is substituted at a position adjacent to a nitrogen atom on itscycle.

Another embodiment of the invention is the provision of a compound ofFormula II or IIA where the various moieties are independently selected,Ar is aryl and R is substituted at a position adjacent to a nitrogenatom on its cycle.

Another embodiment of the invention is the provision of a compound ofFormula II or IIA where the various moieties are independently selected,Ar is phenyl and R is substituted at a position adjacent to a nitrogenatom on its cycle.

Another embodiment of the invention is the provision of a compound ofFormula II or IIA where the various moieties are independently selected,Ar is 5 or 6 membered heteroaryl and R is substituted at a positionadjacent to a nitrogen atom on its cycle.

Another embodiment of the invention is the provision of a compound ofFormula II or IIA where the various moieties are independently selected,Ar is pyridine and R is substituted at a position adjacent to a nitrogenatom on its cycle.

Another embodiment of the invention is the provision of a compound ofFormula II or IIA where the various moieties are independly selected, R¹is —NHR⁴ and R⁴ is cycloalkyl, heterocycloalkyl, aryl or heteroaryl.

Another embodiment of the invention is the provision of a compound ofFormula III or IIIA where the various moieties are independly selected,Ar is aryl, R¹ is —NHR⁴ and R⁴ is cycloalkyl, heterocycloalkyl, aryl orheteroaryl.

Another embodiment of the invention is the provision of a compound ofFormula II or IIA where the various moieties are independly selected, Aris phenyl, R¹ is —NHR⁴ and R⁴ is cycloalkyl, heterocycloalkyl, aryl orheteroaryl.

Another embodiment of the invention is the provision of a compound ofFormula II or IIA where the various moieties are independly selected, Aris 5 or 6 membered heteroaryl, R¹ is —NHR⁴ and R⁴ is cycloalkyl,heterocycloalkyl, aryl or heteroaryl.

Another embodiment of the invention is the provision of a compound ofFormula II or IIA where the various moieties are independly selected, Aris pyridine, R¹ is —NHR⁴ and R⁴ is cycloalkyl, heterocycloalkyl, aryl orheteroaryl.

Another embodiment of the invention is the provision of a compound ofFormula II or IIA where the various moieties are independently selectedand R is a 9 to 10 membered bicyclic heteroaryl containing 1,2,3, or 4heteroatoms independently selected from N, S or O, Ar is phenyl and R¹is —NHR⁴ and R⁴ is cycloalkyl, heterocycloalkyl, aryl or heteroaryl.

Another embodiment of the invention is the provision of a compound ofFormula II or IIA where the various moieties are independently selectedand R is a 9 to 10 membered bicyclic heteroaryl containing 1,2,3, or 4heteroatoms independently selected from N, S or O, Ar is pyridine and R¹is —NHR⁴ and R⁴ is cycloalkyl, heterocycloalkyl, aryl or heteroaryl.

Another embodiment of the invention is the provision of a compound ofFormula II or IIA where the various moieties are independently selectedand R¹ is unsubstituted or substituted C₃-C₁₀ cycloalkyl.

Another embodiment of the invention is the provision of a compound ofFormula II or IIA where the various moieties are independly selected, Aris aryl, and R¹ is unsubstituted or substituted C₃-C₁₀ cycloalkyl.

Another embodiment of the invention is the provision of a compound ofFormula II or IIA where the various moieties arc independly selected, Aris phenyl, and R¹ is unsubstituted or substituted C₃-C₁₀ cycloalkyl.

Another embodiment of the invention is the provision of a compound ofFormula II or IIA where the various moieties are independly selected, Aris 5 or 6 membered heteroaryl, and R¹ is unsubstituted or substitutedC₃-C₁₀ cycloalkyl.

Another embodiment of the invention is the provision of a compound ofFormula II or IIA where the various moieties are independly selected, Aris pyridine, and R¹ is unsubstituted or substituted C₃-C₁₀ cycloalkyl.

Another embodiment of the invention is the provision of a compound ofFormula II or IIA where the various moieties are independently selectedand R¹ is unsubstituted or substituted aryl.

Another embodiment of the invention is the provision of a compound ofFormula II or IIA where the various moieties are independently selectedand R¹ is unsubstituted or substituted 5 to 11 membered monocyclic orbicyclic heterocycloalkyl comprising 1,2,3, or 4 heteroatom(s) selectedfrom N, S or O.

Another embodiment of the invention is the provision of a compound ofFormula II or IIA where the various moieties are independently selected,Ar is aryl and R¹ is unsubstituted or substituted 5 to 11 memberedmonocyclic or bicyclic heterocycloalkyl comprising 1, 2, 3, or 4heteroatom(s) selected from N, S or O.

Another embodiment of the invention is the provision of a compound ofFormula II or IIA where the various moieties are independently selected,Ar is phenyl and R¹ is unsubstituted or substituted 5 to 11 memberedmonocyclic or bicyclic heterocycloalkyl comprising 1, 2, 3, or 4heteroatom(s) selected from N, S or O.

Another embodiment of the invention is the provision of a compound ofFormula II or IIA where the various moieties are independently selected,Ar is 5 or 6 membered heteroaryl and R¹ is unsubstituted or substituted5 to 11 membered monocyclic or bicyclic heterocycloalkyl comprising 1,2, 3, or 4 heteroatom(s) selected from N, S or O.

Another embodiment of the invention is the provision of a compound ofFormula II or IIA where the various moieties are independently selected,Ar is pyridine and R¹ is unsubstituted or substituted 5 to 11 memberedmonocyclic or bicyclic heterocycloalkyl comprising 1, 2, 3, or 4heteroatom(s) selected from N, S or O.

Another embodiment of the invention is the provision of a compound ofFormula II or IIA where the various moieties are independently selected,R¹ is unsubstituted or substituted 5 to 11 membered monocyclic orbicyclic heterocycloalkyl containing at least one N-heteroatom fromwhich the heterocycloalkyl is attached to the rest of the compound ofFormula II or IIA.

Another embodiment of the invention is the provision of a compound ofFormula II or IIA where the various moieties are independently selected,Ar is aryl and R¹ is unsubstituted or substituted 5 to 11 memberedmonocyclic or bicyclic heterocycloalkyl containing at least oneN-heteroatom from which the heterocycloalkyl is attached to the rest ofthe compound of Formula II or IIA.

Another embodiment of the invention is the provision of a compound ofFormula II or IIA where the various moieties are independently selected,Ar is phenyl and R¹ is unsubstituted or substituted 5 to 11 memberedmonocyclic or bicyclic heterocycloalkyl containing at least oneN-heteroatom from which the heterocycloalkyl is attached to the rest ofthe compound of Formula II or IIA.

Another embodiment of the invention is the provision of a compound ofFormula II or IIA where the various moieties are independently selected,Ar is 5 or 6 membered heterocyclic aryl and R¹ is unsubstituted orsubstituted 5 to 11 membered monocyclic or bicyclic heterocycloalkylcontaining at least one N-heteroatom from which the heterocycloalkyl isattached to the rest of the compound of Formula II or IIA.

Another embodiment of the invention is the provision of a compound ofFormula II or IIA where the various moieties are independently selected,Ar is pyridine and R¹ is unsubstituted or substituted 5 to 11 memberedmonocyclic or bicyclic heterocycloalkyl containing at least oneN-heteroatom from which the heterocycloalkyl is attached to the rest ofthe compound of Formula II or IIA.

One embodiment of Formula IIA are compounds where Ar is phenyl and theformula becomes Formula IIB

wherein:

-   R is bicyclic heteroaryl comprising 1, 2, 3 or 4 heteroatom(s)    independently selected from N, S or O, wherein said heteroaryl may    be substituted by one or more substituents selected from the group    consisting of amino, oxo, and halo ; and wherein said heteroaryl can    comprise one or more N-oxide(s) formed with a N atom member of said    heteroaryl;-   R¹ is —NHR⁴ and R⁴ is cycloalkyl, heterocycloalkyl, aryl or    heteroaryl;    -   cycloalkyl;    -   aryl; or    -   heteroaryl; wherein:    -   each of said cycloalkyl, aryl, or heteroaryl is unsubstituted or        substituted with 1, 2, 3, 4 or 5 substituents which can be the        same or different and are independently selected from the group        consisting of:        -   deuterium, halo, hydroxy, hydroxyalkyl, cyano,            —(CH₂)_(m)NR^(a)R^(b), oxo, alkyl, cyanoalkyl, haloalkyl,            alkoxy, haloalkoxy, alkoxyalkyl-, alkenyl, alkynyl,            alkynylalkoxy, —CONH₂, —S-alkyl, —C(O)NH(alkyl),            —C(O)N(alkyl)₂, —C(O)NH(cycloalkyl), —C(O)NH(aryl),            —C(O)N(aryl)₂, arylalkyl-, arylalkoxy-, aryloxy-,            cycloalkyl, heterocycloalkyl, aryl,            (heterocycloalkyl)alkyl-, (heterocycloalkyl)alkoxy-,            —C(O)heterocycloalkyl, heteroaryl, (heteroaryl)alkyl-,            —S(O)₂-alkyl, —S(O)₂-aryl, —S(O)₂—CH_(z)F_(3−z), —C(O)alkyl,            —N(R⁵)—C(O)-alkyl, —N(R⁵)—C(O)-aryl, —S(O₂)NH₂,            —S(O₂)NH(alkyl), —S(O₂)N(alkyl)₂, —N(H)(SO₂)(alkyl), and            methylenedioxy, wherein each of said cycloalkyl,            heterocycloalkyl, aryl or heteroaryl may be substituted by            one or more halo, cyano, alkyl or alkoxy and;    -   each of said cycloalkyl, heterocycloalkyl, aryl, or heteroaryl        may optionally additionally be fused with independently selected        aryl, heteroaryl, heterocycloalkyl or cycloalkyl to from a        bicyclic or tricyclic group that may be substituted by one or        more halo, cyano, alkyl or alkoxy;-   R² and R³ can be independently selected from the group consisting of    H and deuterium;-   R⁵ is H, alkyl or arylalkyl-;-   R^(a) and R^(b) are independently selected from the group consisting    of H, alkyl, alkoxy, alkoxyalkyl and haloalkyl;-   m is 0, 1, 2, 3, 4, 5 or 6;-   z is 0, 1 or 2.

An embodiment of the invention are compounds of Formula IIB where R isselected from 9 to 10 membered bicyclic heteroaryl groups containing1,2,3 or 4 heteroatoms independently selected from N, S, and O.

Another embodiment of the invention are compounds of Formula IIB, whereR is selected from: benzothiazole, dihydronaphthyridine,dihydropyridopyrimidine, dihydropyrrolopyridine, furopyridine,imidazopyrazine, imidazopyrazole imidazopyridine, imidazopyrimidine,indazole, indole, isoquinoline, naphthyridine, pyrazolopyridine,pyrrolopyridine, tetrazolopyridine, tetrahydroimidazopyridine,tetrahydropyrazolopyridine, thiazolopyridine and thienopyridine.

Another embodiment of the invention are compounds of Formula IIB , whereR is selected from: 1H-pyrazolo[3,4-b]pyridine;1,4,6,7-Tetrahydro-pyrazolo[4,3-c]pyridine;7,8-Dihydro-5H-pyrido[4,3-d]pyrimidine;5,7-Dihydro-pyrrolo[3,4-b]pyridine; 7,8-Dihydro-5H-[1,6]naphthyridine;1,4,6,7-Tetrahydro-imidazo[4,5-c]pyridine;1,8a-dihydroimidazo[1,2-a]pyridine; thieno[3,2-c]pyridine;1H-imidazo[1,2-b]pyrazole; 1H-pyrazolo[3,4-b]pyridine;furo[2,3-c]pyridine; 1H-pyrazolo[3,4-b]pyridine;1H-pyrrolo[3,2-c]pyridine; thieno[2,3-b]pyridine;imidazo[1,2-a]pyrimidine; furo[2,3-c]pyridine; isoquinoline;1H-indazole; imidazo[1,2-a]pyridine; thieno[2,3-c]pyridine;furo[2,3-c]pyridine; 1H-pyrrolo[2,3-c]pyridine; imidazo[1,2-a]pyrazine;1,3-benzothiazole; benzo[d]thiazole; 1H-pyrrolo[2,3-b]pyridine;[1,3]thiazolo[5,4-c]pyridine; [1,2,3,4]tetrazolo[1,5-a]pyridine;1,5-naphthyridine; 1H-indole; 1H-imidazo[4,5-c]pyridine; and1,6-naphthyridine.

Another embodiment of the invention is compounds of Formula IIB where Ris substituted at a position adjacent to a nitrogen atom on its cycle.

Another embodiment of the invention is compounds of Formula IIB whereinR is selected from the group consisting of:

Still another embodiment of the invention is compounds of Formula IIBwhere R¹ is —NHR⁴, R⁴ is cycloalkyl, heterocycloalkyl, aryl orheteroaryl.

Yet another embodiment of the invention is compounds of Formula IIB,where R⁴ is unsubstituted or substituted cycloalkyl.

Another embodiment of the invention is compounds of Formula IIB, whereR⁴ is unsubstituted or substituted heterocycloalkyl.

Another embodiment of the invention is compounds of Formula IIB, whereR⁴ is unsubstituted or substituted aryl.

Yet another embodiment of the invention is compounds of Formula IIB,where R⁴ is unsubstituted or substituted heteroaryl.

Still another embodiment of the invention is compounds of Formula IIB,where R¹ is unsubstituted or substituted C₃-C₁₀-cycloalkyl.

Another embodiment of the invention is compounds of Formula IIB, whereR¹ is unsubstituted or substituted aryl.

One embodiment of the invention is compounds of Formula IIB, where R¹ isunsubstituted or substituted 5 to 10 membered monocyclic or bicyclicheteroaryl comprising 1, 2, 3 or 4 heteroatom(s) selected from N, S orO.

Another embodiment of the invention is compounds of Formula IIB, whereR¹ or R⁴ is selected from the group consisting of: 6-methoxypyridine;2-ethoxy-4-fluorophenyl; 3,4-difluorophenyl; 3,4-dimethoxyphenyl;3,4-dimethoxyphenyl; 3-chloro-5-fluorophenyl; 3-fluoro-4-methoxyphenyl;4-chloro-2-methylphenyl; 4-fluoro-2-methoxyphenyl;4-methoxy-2,5-dimethylphenyl; 4-methylphenyl; 5-chloro-2-ethoxyphenyl;5-fluoro-2-methoxyphenyl; 1-(3-chlorophenyl)-1H-pyrazole;1-(4-fluorophenyl)-1H-pyrazole; 1-(propan-2-yl)-1H-pyrazole;1,3-thiazole; 1,4-dimethyl-1H-imidazole; 1,5-dimethyl-1H-imidazole;1-benzothiophene; 1H-indole; 1-methyl-1H-1,3-benzodiazole;1-methyl-1H-indazole; 1-methyl-1H-indole; 1-methyl-1H-pyrazole;1-methyl-3-(trifluoromethyl)-1H-pyrazole;1-methyl-5-(trifluoromethyl)-1H-pyrazole; 1-propyl-1H-pyrazole;2-(2,2,2-trifluoroethoxy)-4-(trifluoromethyl)phenyl;2-(3-fluorophenyl)-1,3-thiazole;2-(benzyloxy)-5-(trifluoromethyl)phenyl; 2-(benzyloxy)phenyl;2-(dimethylamino)pyrimidine; 2-(dimethylcarbamoyl)phenyl;2-(ethoxymethyl)phenyl; 2-(methylsulfamoyl)phenyl;2-(morpholin-4-yl)pyridine; 2-(morpholin-4-yl)pyridine;2-(morpholin-4-ylmethyl)phenyl; 2-(pyrrolidin-1-yl)-1,3-thiazole;2-(trifluoromethoxy)phenyl; 2-(trifluoromethoxy)phenyl];2-(trifluoromethyl)imidazo[1,2-a]pyridine; 2-(trifluoromethyl)phenyl;2-(trifluoromethyl)pyridine; 2,3,6-trimethoxyphenyl;2,3-difluoro-6-methoxyphenyl; 2,3-difluorophenyl;2,3-dihydro-1,4-benzodioxine; 2,3-dihydro-1-benzofuran;2,3-dihydro-1-benzofuranphenyl; 2,3-dimethoxy-5-methylphenyl;2,3-dimethoxyphenyl; 2,3-dimethylphenyl; 2,4,5-trimethylphenyl;2,4-bis(trifluoromethyl)phenyl; 2,4-dichloro-3-methoxyphenyl;2,4-difluorophenyl;2,4-dimethoxyphenyl; 2,4-dimethylphenyl;2,5-difluorophenyl; 2,5-dimethoxyphenyl; 2,5-dimethylphenyl;2,6-dichloro-3-methylphenyl; 2,6-dichlorophenyl;2,6-dimethoxy-4-methylphenyl; 2,6-dimethoxypyridine; 2,6-dimethylphenyl;2-[ethyl(methyl)amino]-1,3-thiazole; 2-acetylphenyl;2-butoxy-4-fluorophenyl; 2-butoxy-5-chlorophenyl;2-butoxy-6-fluorophenyl; 2-chloro-3-(trifluoromethyl)phenyl;2-chloro-3-fluorophenyl; 2-chloro-4-(trifluoromethyl)phenyl;2-chloro-4-fluorophenyl; 2-chloro-4-methoxyphenyl;2-chloro-4-methylphenyl; 2-chloro-5-(hydroxymethyl)phenyl;2-chloro-5-(trifluoromethoxy)phenyl; 2-chloro-5-(trifluoromethyl)phenyl;2-chloro-5-fluorophenyl; 2-chloro-5-methoxyphenyl;2-chloro-5-methoxyphenyl; 2-chloro-5-methylphenyl;2-chloro-6-fluorophenyl; 3-trifluoromethylphenyl;2-chloro-6-methoxyphenyl; 2-chlorophenyl; 2-cyanophenyl;2-ethoxy-4-fluorophenyl; 2-ethoxy-6-fluorophenyl; 2-ethoxyphenyl;2-ethylphenyl; 2-fluoro-3-(propan-2-yloxy)phenyl;2-fluoro-3-(trifluoromethoxy)phenyl; 2-fluoro-3-methoxyphenyl;2-fluoro-3-methylphenyl; 2-fluoro-4-(1H-pyrazol-1-yl)phenyl;2-fluoro-4-(trifluoromethyl)phenyl; 2-fluoro-4-methoxyphenyl;2-fluoro-4-methylphenyl; 2-fluoro-5-methoxyphenyl;2-fluoro-5-methylphenyl; 2-fluoro-6-methoxyphenyl;2-fluoro-6-propoxyphenyl; 2-fluorophenyl; 2H-1,3-benzodioxole;2-methanesulfonamidophenyl; 2-methanesulfonylphenyl;2-methoxy-3-(trifluoromethyl)phenyl;2-methoxy-4-(1H-pyrazol-1-yl)phenyl;2-methoxy-4-(trifluoromethyl)phenyl; 2-methoxy-5-(propan-2-yl)phenyl;2-methoxy-5-(trifluoromethoxy)phenyl; 2-methoxy-5-methylphenyl;2-methoxy-6-(propan-2-yloxy)phenyl; 2-methoxyphenyl;2-methyl-1,3-thiazole; 2-methyl-2H-indazole;2-methyl-4-(1H-pyrazol-1-yl)phenyl; 2-methyl-4-(trifluoromethyl)phenyl;2-methyl-4-propoxyphenyl; 2-methylphenyl; 2-methylpyridine;2-phenoxyphenyl; 2-phenylethane; 3-(1H-pyrazol-1-yl)phenyl;3-(2,2,2-trifluoroethoxy)phenyl; 3-(2-methylpropoxy)phenyl;3-(3,5-dimethyl-1H-pyrazol-1-yl)phenyl; 3-(4-fluorophenoxy)phenyl;3-(5-methyl-1,2,4-oxadiazol-3-yl)phenyl; 3-(cyclopentylcarbamoyl)phenyl;3-(diethylcarbamoyl)-5-fluorophenyl; 3-(difluoromethoxy)phenyl;3-(dimethylsulfamoyl)phenyl; 3-(ethanesulfonyl)phenyl;3-(ethylcarbamoyl)phenyl; 3-(methoxymethyl)phenyl,3-(methylcarbamoyl)phenyl; 3-(morpholin-4-yl)phenyl;3-(piperidin-1-yl)phenyl; 3-(piperidin-1-ylmethyl)phenyl;3-(piperidin-1-ylphenyl; 3-(propan-2-yl)phenyl;3-(propan-2-yloxy)phenyl; 3-(propane-1-sulfonamido)phenyl;3-(pyrimidin-2-yl)phenyl; 3-(trifluoromethoxy)phenyl;3-(trifluoromethyl)phenyl; 3,4-dichlorophenyl; 3,4-dimethoxyphenyl;3,4-dimethylphenyl; 3,5-dichlorophenyl; 3,5-difluorophenyl;3,5-dimethoxyphenyl; 3,5-dimethylphenyl;3-[(2-methylpropyl)carbamoyl]phenyl; 3-[(dimethylamino)methylphenyl;3-[(morpholin-4-yl)carbonyl]phenyl; 3-[(propan-2-yl)carbamoyl]phenyl;3-[2-(dimethylamino)ethoxyphenyl; 3-[2-(dimethylamino)ethyl]phenyl;3-[2-(morpholin-4-yl)ethoxy]phenyl; 3-acetylphenyl; 3-butoxyphenyl;3-chloro-2-(morpholin-4-yl)pyridine; 3-chloro-2-fluorophenyl;3-chloro-2-methoxyphenyl; 3-chloro-2-methylphenyl;3-chloro-4-(trifluoromethyl)phenyl; 3-chloro-4-methoxyphenyl;3-chloro-4-methylphenyl; 3-chloro-4-propoxyphenyl;3-chloro-5-(diethylcarbamoyl)phenyl; 3-chloro-5-(hydroxymethyl)phenyl;3-chloro-5-fluorophenyl; 3-chloro-5-methoxyphenyl;3-chloro-5-methylphenyl; 3-chlorophenyl; 3-cyanophenyl;3-ethoxy-2-fluorophenyl; 3-ethoxy-4-fluorophenyl; 3-ethoxyphenyl;3-ethylphenyl; 3-fluoro-2-methoxyphenyl; 3-fluoro-2-methylphenyl;3-fluoro-2-methylphenyl; 3-fluoro-4-(1H-pyrazol-1-yl)phenyl;3-fluoro-4-(2,2,2-trifluoroethoxy)phenyl;3-fluoro-4-(methylsulfanyl)phenyl; 3-fluoro-4-(trifluoromethoxy)phenyl;3-fluoro-4-(trifluoromethyl)phenyl; 3-fluoro-4-methoxyphenyl;3-fluoro-4-methylphenyl; 3-fluoro-4-propoxyphenyl;3-fluoro-5-(2,2,2-trifluoroethoxy)phenyl;3-fluoro-5-(2-methylpropoxy)phenyl; 3-fluoro-5-(morpholin-4-yl)phenyl;3-fluoro-5-(pyrrolidin-1-yl)phenyl; 3-fluoro-5-(trifluoromethyl)phenyl;3-fluoro-5-methoxyphenyl; 3-fluoro-5-methylphenyl; 3-fluorophenyl;3-hydroxyphenyl; 3-methanesulfonylphenyl; 3-methoxy-4-methylphenyl;3-methoxy-5-methylphenyl; 3-methoxyphenyl; 3-methylphenyl;3-phenylphenyl; 3-phenylpropane; 3-propoxyphenyl; 3-sulfamoylphenyl;3-tert-butylphenyl; 4-(1-cyanocyclopentyl)phenyl;4-(1H-imidazol-1-yl)phenyl; 4-(1H-imidazol-1-ylmethyl)phenyl;4-(1H-pyrazol-1-yl)phenyl; 4-(2-methylpropoxy)phenyl;4-(4-ethoxyphenyl)phenyl; 4-(4-methylpiperazin-1-yl)phenyl;4-(difluoromethyl)-3-fluorophenyl; 4-(dimethylcarbamoyl)phenyl;4-(ethoxymethyl)phenyl; 4-(ethylcarbamoyl)phenyl;4-(hydroxymethyl)phenyl;4-(morpholin-4-yl)phenyl; 4-(propan-2-yl)phenyl;4-(propan-2-yloxy)phenyl; 4-(pyrrolidin-1-yl);4-(pyrrolidin-1-yl)phenyl; 4-(trifluoromethoxy)phenyl;4-(trifluoromethyl)phenyl; 4-(trifluoromethyl)pyridine;3,5-difluorophenyl; 4,5-difluoro-2-methoxyphenyl;4-[(1R)-1-hydroxybutylphenyl; (dimethylamino)methylphenyl;4-[(pyrrolidin-1-yl)carbonyl]phenyl; 4-[2-(dimethylamino)ethyl]phenyl;4-[2-(pyrrolidin-1-yl)ethoxy]phenyl; 4-acetylphenyl;4-butoxy-2-methylphenyl; 4-butoxy-3-chlorophenyl;4-butoxy-3-fluorophenyl; 4-butoxyphenyl; 4-butylphenyl;4-chloro-2-(trifluoromethyl)phenyl; 4-chloro-2-ethoxyphenyl;4-chloro-2-methoxyphenyl; 4-chloro-2-methylphenyl;4-chloro-3-(trifluoromethyl)phenyl; 4-chloro-3-fluorophenyl;4-chloro-3-methoxyphenyl; 4-chlorophenyl; 4-cyanophenyl;4-cyclohexylphenyl; 4-ethoxy-2-methylphenyl; 4-ethoxy-3-fluorophenyl;4-ethoxyphenyl; 4-ethylphenyl; 4-fluoro-2-(propan-2-yloxy)phenyl;4-fluoro-2,5-dimethylphenyl; 4-fluoro-2-methoxyphenyl;4-fluoro-2-methylphenyl; 4-fluoro-3-(2,2,2-trifluoroethoxy)phenyl;4-fluoro-3-(trifluoromethyl)phenyl;4-fluoro-3-[(propan-2-yl)carbamoyl]phenyl; 4-fluoro-3-methoxyphenyl;4-fluoro-3-methylphenyl; 4-fluorophenyl; 4-methane sulfonylphenyl;4-methoxy-2-(trifluoromethyl)phenyl; 4-methoxy-2,5-dimethylphenyl;4-methoxy-2-methylphenyl; 4-methoxy-3,5-dimethylphenyl;4-methoxy-3-methylphenyl; 4-methoxyphenyl; 4-methylphenyl;4-methylpyridine; 4-methylthiophene; 4-phenylbutane; 4-phenylphenyl;4-phenyl-phenyl; 4-propoxyphenyl; 3,5-difluorophenyl;5-(diethylcarbamoyl)-2-fluorophenyl; 5-(dimethylamino)pyrazine;5-(pyrrolidin-1-yl)pyridine; 5-(trifluoromethyl)pyridine;5-acetyl-2-methoxyphenyl; 5-chloro-2-(2,2,2-trifluoroethoxy)phenyl;5-chloro-2-(2,2-di fluoroethoxy)phenyl;5-chloro-2-(prop-2-yn-1-yloxy)phenyl; 5-chloro-2-(propan-2-yloxy)phenyl;5-chloro-2-ethoxyphenyl; 5-chloro-2-hydroxyphenyl;5-chloro-2-methoxyphenyl; 5-chloro-2-methylphenyl;5-chloro-2-propoxyphenyl; 5-chloropyridine; 5-cyano-2-methoxyphenyl;5-fluoro-2-(hydroxymethyl)phenyl; 5-fluoro-2-methoxyphenyl;5-fluoro-2-methylphenyl; 5-fluoro-6-methylpyridine; 5-fluoropyridine;5H,6H,7H,8H,9H-imidazo[1,2-a]azepine;5H,6H,7H,8H,9H-imidazo[1,2-a]azepinephenyl; 5-hydroxy-(4-phenylphenyl);5-hydroxy-1-methyl-1H-indazole; 5-hydroxy-2-(trifluoromethoxy)phenyl;5-hydroxy-3-(morpholin-4-yl)phenyl;5-hydroxy-3-(piperidin-1-ylphenyl;5-hydroxy-3-(pyrrolidin-1-ylphenyl;5-methoxypyridine; 5-methylpyridine; 5-methylthiophene;5-tert-butyl-2-methoxyphenyl; 6-(1H-pyrazol-1-yl)pyridine;6-(3,4-difluorophenyl)pyridine; 6-(4-methylpiperazin-1-yl)pyridine;6-(dimethylamino)pyridine; 6-(morpholin-4-yl)pyridine;6-(trifluoromethyl)pyridine; 6-amino-(3,5-difluorophenyl);6-chloro-2-fluoro-3-methylphenyl; 6-chloroimidazo[1,2-a]pyridine;6-chloroimidazo[1,2-a]pyridinephenyl; 6-methoxynaphthalene;6-methoxypyridine; 6-methylpyrazine; 6-methylpyridine;8-thiatricyclo[7.4.0.0^(2,7)]trideca-1(13),2,4,6,9,11-hexaene;b6-chloroimidazo[1,2-a]pyridine; Cyclohexane; dimethyl-1,3-thiazole;furan; isoquinoline; naphthalene; naphthalenephenyl; phenoxathiine;phenyl; pyridine and quinoline.

Another embodiment of the invention is compounds of Formula IIB, whereR¹ is cycloalkyl, aryl or heteroaryl, wherein each of said cycloalkyl,aryl, or heteroaryl is unsubstituted or substituted with 1, 2, 3, 4 or 5substituents which can be the same or different and are independentlyselected from the group consisting of: halo, hydroxy, hydroxyalkyl,cyano, alkyl, alkynyl, alkynylalkoxy, alkoxyalkyl, alkoxy, haloalkyl,haloalkoxy, —C(O)NH(alkyl), —C(O)NH(cycloalkyl), —C(O)N(alkyl)₂,arylalkoxy-, aryloxy-, cycloalkyl, heterocycloalkyl, aryl,(heterocycloalkyl)alkyl-, (heterocycloalkyl)alkoxy-,—C(O)heterocycloalkyl, heteroaryl, (heteroaryl)alkyl-, —S(O)₂-alkyl,—S-alkyl, —C(O)alkyl, —S(O₂)NH₂, —S(O₂)NH(alkyl), —S(O₂)N(alkyl)₂,—N(H)(SO₂)(alkyl), wherein each of said cycloalkyl, heterocycloalkyl,aryl or heteroaryl may be substituted by one or more halo, cyano, alkylor alkoxy; and z is 0, 1 or 2.

Still another embodiment of the invention is compounds of Formula IIC,where R¹ is cycloalkyl, aryl or heteroaryl, wherein each of saidcycloalkyl, aryl, or heteroaryl is unsubstituted or substituted with 1,2, 3, 4 or 5 substituents which can be the same or different and arcindependently selected from the group consisting of: halo, haloalkyl andhaloalkoxy.

Another embodiment of the invention is compounds of Formula IIB, wherehaloalkyl is —CH_(z)F_(3−z), —CH₂CH_(z)F_(3−z), and z is 0, 1 or 2.

One embodiment of the invention is compounds of Formula IIB, wherehaloalkoxy is —OCH_(z)F_(3−z), and z is 0, 1 or 2.

Another embodiment of the invention is compounds of Formula IIB, wherehalo is F.

Another embodiment of the invention is compounds of Formula IIB, where Ris 1H-pyrazolo[3,4-b]pyridine.

Another embodiment of the invention is compounds of Formula IIB, where Ris 1,8a-dihydroimidazo[1,2-a]pyridine.

Anyone or more embodiments of Formula IIB provided above may be combinedwith one or more other embodiments of Formula IIB as provided above.

In another embodiment, the invention is further illustrated by thecompounds shown in Table 2:

Lengthy table referenced here US20190105307A1-20190411-T00001 Pleaserefer to the end of the specification for access instructions.

EXAMPLES

The following are illustrative, but non-limiting, examples of certainembodiments of the present invention.

The invention is illustrated further by the following examples, whichare not to be construed as limiting the invention in scope or spirit tothe specific procedures described in them. Those having skill in the artwill recognize that the starting materials may be varied and additionalsteps employed to produce compounds encompassed by the presentinventions, as demonstrated by the following examples. In some cases,protection of certain reactive functionalities may be necessary toachieve some of the above transformations. In general, such need forprotecting groups, as well as the conditions necessary to attach andremove such groups, will be apparent to those skilled in the art oforganic synthesis.

Compounds according to the invention may be synthesized by syntheticroutes that include processes analogous to those well-known in thechemical arts, particularly in light of the description containedherein, and those for other heterocycles described in: ComprehensiveHeterocyclic Chemistry II, Editors Katritzky and Rees, Elsevier, 1997,e.g. Volume 3; Liebigs Annalen der Chemie, (9):1910-16, (1985);Helvetica Chimica Acta, 41:1052-60, (1958); Arzneimittel-Forschung,40(12):1328-31, (1990), each of which are expressly incorporated byreference. Starting materials arc generally available from commercialsources such as Aldrich Chemicals (Milwaukee, Wis.) or are readilyprepared using methods well known to those skilled in the art (e.g.,prepared by methods generally described in Louis F. Fieser and MaryFieser, Reagents for Organic Synthesis, v. 1-23, Wiley, N.Y. (1967-2006ed.), or Beilsteins Handbuch der organischen Chemie, 4, Aufl. ed.Springer-Verlag, Berlin, including supplements (also available via theBeilstein online database).

Synthetic chemistry transformations and protecting group methodologies(protection and &protection) useful in synthesizing compounds accordingto the invention and necessary reagents and intermediates are known inthe art and include, for example, those described in R. Larock,Comprehensive Organic Transformations, VCH Publishers (1989); T. W.Greene and P. G. M. Wuts, Protective Groups in Organic Synthesis, 3rdEd., John Wiley and Sons (1999); and L. Paquette, ed., Encyclopedia ofReagents for Organic Synthesis, John Wiley and Sons (1995) andsubsequent editions thereof.

Compounds according to the invention may be prepared singly or ascompound libraries comprising at least 2, for example 5 to 1,000compounds, or 10 to 100 compounds. Libraries of compounds of Formula Imay be prepared by a combinatorial ‘split and mix’ approach or bymultiple parallel syntheses using either solution phase or solid phasechemistry, by procedures known to those skilled in the art. Thusaccording to a further aspect of the invention there is provided acompound library comprising at least 2 compounds, or pharmaceuticallyacceptable salts thereof.

The General Procedures and Examples provide exemplary methods forpreparing compounds according to the invention. Those skilled in the artwill appreciate that other synthetic routes may be used to synthesizethe compounds according to the invention. Although specific startingmaterials and reagents are depicted and discussed in the schemes,General Procedures, and Examples, other starting materials and reagentscan be easily substituted to provide a variety of derivatives and/orreaction conditions. In addition, many of the exemplary compoundsprepared by the described methods can be further modified in light ofthis disclosure using conventional chemistry well known to those skilledin the art.

In preparing compounds according to the invention, protection of remotefunctionality (e.g., primary or secondary amine) of intermediates may benecessary. The need for such protection will vary depending on thenature of the remote functionality and the conditions of the preparationmethods. Suitable amino-protecting groups include acetyl,trifluoroacetyl, t-butoxycarbonyl (BOC), benzyloxycarbonyl (CBz) and9-fluorenylmethyleneoxycarbonyl (Fmoc). The need for such protection isreadily determined by one skilled in the art. For a general descriptionof protecting groups and their use, see T. W. Greene, Protective Groupsin Organic Synthesis, John Wiley & Sons, New York, 1991.

In the methods of preparing compounds according to the invention, it maybe advantageous to separate reaction products from one another and/orfrom starting materials. The desired products of each step or series ofsteps is separated and/or purified to the desired degree of homogeneityby the techniques common in the art. Typically such separations involvemultiphase extraction, crystallization from a solvent or solventmixture, distillation, sublimation, or chromatography. Chromatographycan involve any number of methods including, for example: reverse-phaseand normal phase; size exclusion; ion exchange; high, medium and lowpressure liquid chromatography methods and apparatus; small scaleanalytical; simulated moving bed (SMB) and preparative thin or thicklayer chromatography, as well as techniques of small scale thin layerand flash chromatography.

Another class of separation methods involves treatment of a mixture witha reagent selected to bind to or render otherwise separable a desiredproduct, unreacted starting material, reaction by product, or the like.Such reagents include adsorbents or absorbents such as activated carbon,molecular sieves, ion exchange media, or the like. Alternatively, thereagents can be acids in the case of a basic material, bases in the caseof an acidic material, binding reagents such as antibodies, bindingproteins, selective chelators such as crown ethers, liquid/liquid ionextraction reagents (LIX), or the like. Selection of appropriate methodsof separation depends on the nature of the materials involved, such as,boiling point and molecular weight in distillation and sublimation,presence or absence of polar functional groups in chromatography,stability of materials in acidic and basic media in multiphaseextraction, and the like.

Diastereomeric mixtures can be separated into their individualdiastereomers on the basis of their physical chemical differences bymethods well known to those skilled in the art, such as bychromatography and/or fractional crystallization. Enantiomers can beseparated by converting the enantiomeric mixture into a diastereomericmixture by reaction with an appropriate optically active compound (e.g.,chiral auxiliary such as a chiral alcohol or Mosher's acid chloride),separating the diastereomers and converting (e.g., hydrolyzing) theindividual diastereoisomers to the corresponding pure enantiomers. Also,some of the compounds of the present invention may be atropisomers(e.g., substituted biaryls) and are considered as part of thisinvention. Enantiomers can also be separated by use of a chiral HPLCcolumn.

A single stereoisomer, e.g., an enantiomer, substantially free of itsstereoisomer may be obtained by resolution of the racemic mixture usinga method such as formation of diastereomers using optically activeresolving agents (Eliel, E. and Wilen, S. “Stereochemistry of OrganicCompounds,” John Wiley & Sons, Inc., New York, 1994; Lochmuller, C. H.,(1975) J. Chromatogr., 113(3):283-302). Racemic mixtures of chiralcompounds of the invention can be separated and isolated by any suitablemethod, including: (1) formation of ionic, diastereomeric salts withchiral compounds and separation by fractional crystallization or othermethods, (2) formation of diastereomeric compounds with chiralderivatizing reagents, separation of the diastereomers, and conversionto the pure stereoisomers, and (3) separation of the substantially pureor enriched stereoisomers directly under chiral conditions. See: “DrugStereochemistry, Analytical Methods and Pharmacology,” Irving W. Wainer,Ed., Marcel Dekker, Inc., New York (1993).

Under method (1), diastereomeric salts can be formed by reaction ofenantiomerically pure chiral bases such as brucine, quinine, ephedrine,strychnine, a-methyl-b-phenylethylamine (amphetamine), and the like withasymmetric compounds bearing acidic functionality, such as carboxylicacid and sulfonic acid. The diastereomeric salts may be induced toseparate by fractional crystallization or ionic chromatography. Forseparation of the optical isomers of amino compounds, addition of chiralcarboxylic or sulfonic acids, such as camphorsulfonic acid, tartaricacid, mandelic acid, or lactic acid can result in formation of thediastereomeric salts.

Alternatively, by method (2), the substrate to be resolved is reactedwith one enantiomer of a chiral compound to form a diastereomeric pair(E. and Wilen, S. “Stereochemistry of Organic Compounds”, John Wiley &Sons, Inc., 1994, p. 322). Diastereomeric compounds can be formed byreacting asymmetric compounds with enantiomerically pure chiralderivatizing reagents, such as menthyl derivatives, followed byseparation of the diastereomers and hydrolysis to yield the pure orenriched enantiomer. A method of determining optical purity involvesmaking chiral esters, such as a menthyl ester, e.g., (-) menthylchloroformate in the presence of base, or Mosher ester,a-methoxy-a-(trifluoromethyl)phenyl acetate of the racemic mixture andanalyzing the 1H NMR spectrum for the presence of the two atropisomericenantiomers or diastereomers (Jacob III. J. Org. Chem. (1982) 47:4165).Stable diastereomers of atropisomeric compounds can be separated andisolated by normal- and reverse-phase chromatography following methodsfor separation of atropisomeric naphthyl-isoquinolines (WO 96/15111). Bymethod (3), a racemic mixture of two enantiomers can be separated bychromatography using a chiral stationary phase (“Chiral LiquidChromatography” (1989) W. J. Lough, Ed., Chapman and Hall, New York;Okamoto, J. Chromatogr., (1990) 513:375-378). Enriched or purifiedenantiomers can be distinguished by methods used to distinguish otherchiral molecules with asymmetric carbon atoms, such as optical rotationand circular dichroism.

Definitions Used in the Following Schemes and Elsewhere Herein are:

-   -   BOP ammonium 4-(3-(pyridin-3-methyl)ureido)benzenesulfinate    -   CDCl₃ deuterated chloroform    -   δ chemical shift (ppm)    -   DCM dichloromethane or methylene chloride    -   DIEA N,N-diisopropylethylamine    -   DMA N,N-dimethylacetamide    -   DMF N,N-dimethylformamide    -   DMSO dimethylsulfoxide    -   DMSO-d₆ deuterated dimethylsulfoxide    -   EDCl        N1-((ethylimino)methylene)-N3,N3-dimethylpropane-1,3-diamine        hydrochloride    -   EtOAc ethyl acetate    -   EtOH ethanol    -   GF/F glass microfiber filter    -   ¹H NMR proton nuclear magnetic resonance    -   HOAc acetic acid    -   HATU        2-(3H-[1,2,3]triazolo[4,5-b]pyridin-3-yl)-1,1,3,3-tetramethylisouronium        hexafluorophosphate    -   HOBT 1H-benzo[d][1,2,3]triazol-1-ol hydrate    -   HPLC high pressure liquid chromatography    -   MHz megahertz    -   KOAc potassium acetate    -   i-PrOH isopropanol    -   LC-MS liquid chromatography/mass spectrometry    -   (M+1) mass+1    -   m-CPBA m-chloroperbenzoic acid    -   MeOH methanol    -   N₂ nitrogen    -   NaHCO₃ sodium bicarbonate    -   MgSO₄ magnesium sulfate    -   PTLC preparative thin layer chromatography    -   TEA triethylamine    -   THF tetrahydrofuran    -   TLC thin layer chromatography

Amide-Sulfonamide:

In Scheme 1, compound III can be obtained by treating II with I (G=OH)in the presence of a coupling reagent such as EDCl, HATU, or HOBt, and abase (e.g.: K₂CO₃, Cs₂CO₃, NR₁R₂R₃, NaOR, KOR) in an inert solvent suchas dichloromethane, N,N-dialkylformamide, N,N-dialkylacetamide,dialkylethers, cyclic ethers, DMSO, N-methyl-2-pyrrolidinone attemperatures ranging from −78° C. to 200° C. Alternatively, compound Ican be treated with I (G=OR) in the presence of trimethylaluminum in aninert solvent (such as toluene) at temperatures ranging from −78° C. to200° C.

Those having skill in the art will recognize that the starting materialsmay be varied and additional steps employed to produce compoundsencompassed by the present inventions, as demonstrated by the followingexamples. Unless otherwise specified, all reagents and solvents were ofstandard commercial grade and were used without further purification.

Amide Sulfone:

Compound III of scheme 2 can be obtained by treating II with I (G=OH) inthe presence of a coupling reagent such as EDCl, HATU, BOP, or HOBt, anda base (eg: K₂CO₃, Cs₂CO₃, NR₁R₂R₃, NaOR, KOR) in an inert solvent suchas dichloromethane, N,N-dialkylformamide, N,N-dialkylacetamide,dialkylethers, DMSO, or N-methyl-2-pyrrolidinone at temperatures rangingfrom −78° C. to 200° C. Alternatively, compound III can be obtained bytreating I (G=OR) with I and trimethylaluminum in an inert solvent (suchas toluene) at temperatures ranging from −78° C. to 200° C.

Those having skill in the art will recognize that the starting materialsmay be varied and additional steps employed to produce compoundsencompassed by the present inventions, as demonstrated by the followingexamples. Unless otherwise specified all reagents and solvent are ofstandard commercial grade and are used without further purification.

In Scheme 3, the compound of III present invention can also besynthesized by following the steps outlined in Scheme IV. Treating IIwith IV in the presence of a coupling reagent such as EDCl, HATU, BOP,or HOBt, and a base (eg: K₂CO₃, Cs₂CO₃, NR₁R₂R₃, NaOR, KOR) in an inertsolvent such as dichloromethane, N,N-dialkylformamide,N,N-dialkylacetamide, dialkylethers, DMSO, or N-methyl-2-pyrrolidinoneat temperatures ranging from −78° C. to 200° C. gives compound V.Compound V can be treated with a base such as sodium ethoxide in thepresent of a protonated solvent such as ethanol to afford compound VI.Treating compound VI with arylboronic acid or aryl halogens facilitatedby palladium or copper to obtain the target compound III.

Example 1 Preparation of Representative Amide-Sulfonamide Analogues

These examples illustrate the preparation of representative substitutedamide-sulfonamide analogues.

Example 1AN-(4-(N-(2-(trifluoromethoxy)phenyl)sulfamoyl)benzyl)-1H-pyrrolo[3,2-c]pyridine-2-carboxamide

A: 4-cyano-N-(2-(trifluoromethoxy)phenyl)benzenesulfonamide

2-(Trifluoromethoxy)aniline (10.902 g, 58.5 mmol) was dissolved inpyridine (100 mL) and cooled to 0° C. A solution of4-cyanobenzene-1-sulfonyl chloride (11.573 g, 55.7 mmol) was added inpyridine (100 mL) over 10 minutes via addition funnel. The mixture washeated to 85° C. for 16 hours and the pyridine was removed under reducedpressure. The residue was diluted with DCM and washed with 1M HCl (×2),water (×1), brine (×1), and saturated NaHCO₃ (×1). The organic layer wasdried over anhydrous MgSO₄, filtered, concentrated, and purified byBiotage SP1 (hexanes/DCM) to afford the title compound as a white solid.

¹H NMR (300 HMz; DMSO-d₆): δ 10.58 (s, 1H), 8.06 (d, 2H), 7.89 (d, 2H),7.30 (s, 4H).

B: 4-(aminomethyl)-N-(2-(trifluoromethoxy)phenyl)benzenesulfonamide

4-Cyano-N-(2-(trifluoromethoxy)phenyl)benzenesulfonamide (2.0 g, 5.84mmol) was dissolved in THF (30 mL) and borane tetrahydrofuran complex(14.61 mL of a 1M solution in THF) was added. The mixture was heated to70° C. for 2 hours, then cooled to room temperature followed by theaddition of MeOH (10 mL). The mixture was briefly warmed to 70° C. for15 minutes, then the volatiles removed under reduced pressure and EtOAc(100 mL) and 1N NaOH (50 mL) were added to the residue. The layers wereseparated, and the organic layer washed with water and brine. Thecombined aqueous washes were extracted with EtOAc, combined with theprevious organic extracts, and dried over MgSO₄. The residue waspurified by Biotage SP1 (McOH/DCM/NH₃ gradient) to afford the titlecompound as a pale yellow solid.

¹H NMR (300 HMz; DMSO-d₆): δ 7.70 (d, 2H), 7.41 (d, 2H), 7.19 (d, 1H),7.00 (d, 1H), 6.89 (t, 1H), 6.58 (t, 1H), 3.84 (s, 2H).

C:N-(4-(N-(2-(trifluoromethoxy)phenyl)sulfamoyl)benzyl)-1H-pyrrolo[3,2-c]pyridine-2-carboxamide

A mixture of 1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid (478 mg, 2.95mmol), 4-(aminomethyl)-N-(2-(trifluoromethoxy)phenyl)benzenesulfonamide(973 mg, 2.81 mmol), HATU (1.122 g, 2.95 mmol), DIEA (1.082 mL, 6.20mmol), and DMF (15 mL) at 25° C. were stirred for 16 hours at ambienttemperature. The mixture was diluted with EtOAc and washed successivelywith saturated NaHCO₃ and brine. The organic extracts were separated anddried over MgSO₄, filtered, concentrated, and purified by Biotage SP1(DCM/MeOH gradient). The combined fractions were triturated with Et₂O toafford the product as a white solid.

¹H NMR (300 HMz; DMSO-d₆): δ 12.10 (br s, 1H), 9.23 (t, 1 H), 8.98 (s,1H), 8.21 (d, 1H), 7.78 (d, 2H), 7.47 (d, 2H), 7.38 (d, 1H), 7.31-7.19(m, 6H), 4.58 (d, 2H). LC-MS: 491.11 (M+1).

Example 1BN-(4-(piperidin-1-ylsulfonyl)benzyl)thieno[3,2-c]pyridine-2-carboxamide

(4-(Piperidin-1-ylsulfonyl)phenyl)methanamine (155 mg, 0.609 mmol) andtrimethylaluminum (0.30 mL, 0.600 mmol) were combined in toluene (2 mL)and stirred for 30 minutes at ambient temperature. A solution of methylthieno[3,2-c]pyridine-2-carboxylate (100 mg, 0.518 mmol, preparedaccording to WO 2004/064836) in toluene (2 mL) was then added and themixture heated to 110° C. for 16 hours. Upon cooling, a saturatedsolution of potassium sodium tartrate and EtOAc were added and themixture stirred vigorously for 30 minutes and then filtered. The layerswere separated, the organics dried over MgSO₄, and purified by BiotageSP1 (100% EtOAc) to afford the title compound as white foam.

¹H NMR (300 HMz; CDCl₃): δ 9.13 (s, 1H), 8.50 (d, 1H), 7.93 (s, 1H),7.79 (t, 1H), 7.67 (d, 1H), 7.48 (d, 2H), 7.36 (d, 2H), 4.69 (d, 2H),2.89 (t, 4H), 1.63-1.55 (m, 4H), 1.42-1.34 (m, 2H) LC-MS: 416.11 (M+1).

Example 1CN-(4-(N-(2,5-dimethoxyphenyl)sulfamoyl)benzyl)-1H-pyrrolo[3,2-c]pyridine-2-carboxamide

A: N-(4-(N-(2,5-dimethoxyphenyl)sulfamoyl)benzyl)acetamide

A mixture of 4-(acetamidomethyl)benzene-1-sulfonyl chloride (25 mg, 0.1mmol), 2,5-dimethoxyaniline (15.3 mg, 0.1 mmol), and pyridine (0.25 mL)in DMA (1 mL) were heated at 50° C. for 16 hours before beingconcentrated under reduced pressure. The residue was purified by PTLC(100% EtOAc) to afford the title compound as white solid.

¹H NMR (400 HMz; CDCl₃): δ 7.73 (d, J=8 Hz, 2H), 7.30 (d, J=8 Hz, 2H),7.14 (d, J=3.2 Hz, 1H), 7.05 (s, 1H), 6.66 (d, J=8.8 Hz, 1H), 6.54 (d d,J=8.8 Hz, J′=3.2 Hz, 1H), 5.95 (br s, 1H), 4.46 (d, J=6 Hz, 2H), 3.74(s, 3H), 3.61 (s, 3H), 2.07 (s, 3H). LC-MS: 364.99 (M+1).

B: (4-(N-(2,5-dimethoxyphenyl)sulfamoyl)phenyl)methanaminium chloride

A mixture of N-(4-(N-(2,5-dimethoxyphenyl)sulfamoyl)benzyl)acetamide (28mg, 0.077 mmol) and 3N HCl (0.5 mL, 1.5 mmol) in 70% i-PrOH (0.5 mL) washeated at 100° C. for 5 hours. The mixture was concentrated to drynessin vacuo to afford the title compound as off-white solid.

¹H NMR (400 HMz; CDCl₃): δ 7.84 (d, J=8.4 Hz, 2H), 7.56 (d, J=8.8 Hz,2H), 7.04 (d, J=2.8 Hz, 1H), 6.74 (d, J=9.2 Hz, 1H), 6.60 (dd, J=9.2 Hz,J′=3.2 Hz, 1H), 5.95 (br s, 1H), 4.16 (s, 2H), 3.70 (s, 3H), 3.54 (s,3H). LC-MS: 323.03 (M+1)

C:N-(4-(N-(2,5-dimethoxyphenyl)sulfamoyl)benzyl)-1H-pyrrolo[3,2-c]pyridine-2-carboxamide

The title compound was prepared following Example 1C, substituting BOPin place of HATU, and4-(aminomethyl)-N-(2,5-dimethoxyphenyl)benzenesulfonamide in place of4-(aminomethyl)-N-(2-(trifluoromethoxy)phenyl)benzenesulfonamide. Theproduct was purified by PTLC.

¹H NMR (400 HMz; CD₃OD): δ 8.90 (d, J=0.8 Hz, 1H), 8.22 (d, J=5.6 Hz,1H), 7.71 (d, J=8.4 Hz, 2H), 7.51 (d, J=6 Hz, 1H), 7.45 (d, J=8.8 Hz,2H), 7.28 (d, J=0.8 Hz, 1H), 7.02 (d, J=3.2 Hz, 1H), 6.70 (d, J=9.2 Hz,1H), 6.59 (dd, J=8.8 Hz, J′=3.2 Hz, 1H), 4.62 (s, 2H), 3.69 (s, 3H),3.46 (s, 3H). LC-MS: 466.98 (M+1).

Example 2 Preparation of Representative Amide-Sulfone Analogues

These examples illustrate the preparation of representative substitutedamide-sulfonamide analogues.

Example 2AN-(4-(phenylsulfonyl)benzyl)-1H-pyrrolo[3,2-c]pyridine-2-carboxamide

a: 4-(phenylsulfonyl) benzonitrile

A mixture of 4-fluorobenzonitrile (5 g, 41.3 mmol) and sodiumbenzenesulfinate (7.45 g, 45.4 mmol) in DMSO (30 mL) was heated at 130°C. for 16 hours. The mixture was cooled to room temperature and pouredonto 300 g of ice. The precipitate was collected, washed with water, anddried to afford the title compound.

¹H NMR (300 MHz, CDCl₃): δ 8.03-8.07 (m, 2H), 7.93-7.97 (m, 2H),7.78-7.82 (m, 2H), 7.60 (m7.65, 1H), 7.26-7.58 (m, 2H)

b: (4-[phenylsulfonyl]phenyl)methanamine

A mixture of 4-(phenylsulfonyl) benzonitrile (9.4 g, 38.64 mmol) andRaney Ni (500 mg) in 2N NH₃—MeOH (150 mL) was hydrogenated for 16 hoursat 50 psi. Nitrogen gas was bubbled through the mixture, which was thenfiltered through a short Celite pad, and washed with methanol. Thefiltrate was concentrated and triturated with ether to afford the titlecompound.

¹H NMR (300 MHz, DMSO-d₆): δ 7.85-7.95 (m, 4H), 7.53-7.68 (m, 5H), 3.74(s, 2H), 1.83 (br s, 2H)

c: N-(4-(phenylsulfonyl)benzyl)-1H-pyrrolo[3,2-c]pyridine-2-carboxamide

A mixture of 1H-pyrrolo[3,2-2]pyridine-2-carboxlic acid (1.0 g, 6.17mmol), HATU (3.52 g, 9.25 mmol), diisopropylethylamine (2.69 mL, 15.42mmol), and (4-(phenylsulfonyl)phenyl)methanamine (1.754 g, 7.09 mmol) inDMF (70 mL) was stirred at room temperature for 16 hours. The solventwas removed under reduced pressure, water (200 mL) was added, and themixture was extracted with EtOAc (3×300 mL). The combined organic layerswere successively washed with water, saturated sodium bicarbonate, andbrine. The extracts were dried with sodium sulfate, concentrated invacuo, and purified by Biotage with MeOH/DCM (0%-10%) to afford thetitle compound.

¹H NMR (300 MHz, DMSO-d₆) δ 4.56 (d, J=5.57 Hz, 2H), 7.29 (s, 1H), 7.34(d, J=5.57 Hz, 1H), 7.56-7.66 (m, 5H), 7.91-7.94 (m, 4H), 8.20 (d,J=5.87 Hz, 1H), 8.91 (s, 1H), 9.245-9.28 (m, 1H). 12.03 (s, 1H) LC-MS:392.13 (M+1).

Example 2B3-bromo-N-(4-(phenylsulfonyl)benzyl)-1H-Pyrrolo[3,2-c]pyridine-2-carboxamide

A mixture ofN-(4-(phenylsulfonyl)benzyl)-1H-pyrrolo[3,2-c]pyridine-2-carboxamide(from Example 1; 200 mg, 0.511 mmol) and 1-bromopyrrolidine-2,5-dione(91 mg, 0.511 mmol) in DMF (10 mL) was stirred at room temperature for16 hours. EtOAc (100 mL) was added to the mixture. The organic layer waswashed with water and brine, dried with sodium sulfate, and concentratedin vacuo. The crude was purified by Biotage with McOH/DCM (0%-10%) toafford the title compound.

¹H NMR (300 MHz, DMSO-d₆): δ 12.42 (br s, 1H), 8.78 (m, 2H), 8.30 (d,1H), 7.93 (d, 4H), 7.59-7.69 (m, 5H), 7.38 (dd, 1H), 4.59(d, 2H) LC-MS:470.06 (M+1).

Example 2CN-({4-[(4-fluorobenzene)sulfonyl]phenyl}methyl)thieno[2,3-c]pyridine-2-carboxamide

a: 4-(4-fluorophenylsulfonyl) benzonitrile

The title compound was prepared following Example 1A, substitutingsodium 4-fluorobenzenesulfinate for sodium benzenesulfinate.

¹H NMR (300 MHz, DMSO-D₆): δ 8.10-8.18 (m, 6H), 7.42-7.12 (t, 2H).

b: (4-[4-fluorophenylsulfonyl]phenyl) methanamine

The title compound was prepared following Example 1B, substituting4-(4-fluorophenylsulfonyl)benzonitrile for4-(phenylsulfonyl)benzonitrile.

¹H NMR (300 MHz, (DMSO-d₆): δ 7.8-7.96 (m, 4H), 3.74 (s, 2H), 7.42-7.64(m, 4H), 3.64 (m, 2H).

c:N-({4-[(4-fluorobenzene)sulfonyl]phenyl}methyl)thieno[2,3-c]pyridine-2-carboxamide

(4-(4-Fluorophenylsulfonyl)phenyl)methanamine hydrochloride (1409 mg,4.67 mmol) was mixed with toluene (20 mL) and cooled to 0° C.Trimethylaluminum (7.00 mL of a 2M solution in toluene) was added andthe mixture was stirred for 40 minutes at ambient temperature. Asolution of methyl thieno[2,3-c]pyridine-2-carboxylate (820 mg, 4.24mmol, prepared according to WO 2004/064836) in toluene (10 mL) was addedvia syringe, and the mixture was heated to 80° C. for 4 hours. Themixture was diluted with saturated potassium sodium tartrate (25 mL) andEtOAc (25 mL), stirred vigorously for 1 hour, and then filtered throughGF/F paper. The organic layer was separated, dried over MgSO₄, filtered,and concentrated to a yellow solid. The residue was triturated with DCMand the title compound was collected by vacuum filtration.

¹H NMR (300 MHz, DMSO-d₆) δ 9.59 (t, 1H), 9.30 (s, 1H), 9.50 (d, 1H),8.15 (s, 1H), 8.04-7.98 (m, 2H), 7.96-7.90 (m, 3H), 7.56 (d, 2H),7.47-7.40 (m, 2H), 4.55 (d, 2H)

LC-MS: 427.03 (M+1).

Example 2DN-(4-(phenylsulfonyl)benzyl)-1H-pyrrolo[3,2-c]pyridine-2-carboxamide

a: sodium 4-(acetamidomethyl)benzenesulfinate

4-(Acetamidomethyl)benzene-1-sulfonyl chloride (1.24 g, 5 mmol) wasadded to a water-cooled solution of Na₂SO₃ (1.89 g, 15 mmol) in water(3.75 mL) then solid NaHCO₃ (850 mg, 10 mmol) was added in several smallportions to keep the pH slightly basic. The mixture was stirred atambient temperature for 2 hours, affording a thick white suspension.Brine (2 ml) was added and the mixture was stirred at ambienttemperature for 15 minutes. The precipitate was collected by filtrationand dried overnight under vacuum. The solid was ground up and stirredwith 125 ml of MeOH for 30 min then the solid was filtered off, washingwith MeOH (20 mL). The filtrate was concentrated to give the titlecompound as a white solid.

¹H NMR (400 MHz, CD₃OD): δ 7.61 (d, J=8.4 Hz, 2H), 7.34 (d, J=8.4 Hz,2H), 4.38 (s, 2H), 1.98 (s, 3H).

b: N-(4-(benzo[d][1,3]dioxol-5-ylsulfonyl)benzyl)acetamide

A mixture of sodium 4-(acetamidomethyl)benzenesulfinate (23.5 mg, 0.1mmol), benzo[d][1,3]dioxol-5-ylboronic acid (20.7 mg, 0.125 mmol),copper(II) acetate (22.7 mg, 0.125 mmol), and TEA (0.063 mL, 0.45 mmol)in DMSO (1.5 mL) was heated at 60° C. for 16 hours. The mixture wascooled to room temperature and partitioned between EtOAc-brine. Theorganic layer was separated and concentrated in vacuo. The crude waspurified by PTLC (100% EtOAc) to afford the title compound as whitesolid.

¹H NMR (400 MHz, CDCl₃): δ 7.85 (d, J=8 Hz, 2H), 7.52 (dd, J=8 Hz,J′=1.6 Hz, 1H), 7.39 (d, J=8.4 Hz, 2H), 7.29 (d, J=2 Hz, 1H), 6.87 (d,J=8 Hz, 1H), 6.05 (s, 2H), 5.87 (br s, 1H), 4.47 (d, J=6.4 Hz, 2H), 2.04(s, 3H).

LC-MS: 333.97 (M+1)

c: (4-(benzo[d][1,3]dioxol-5-ylsulfonyl)phenyl)methanamine hydrochloride

A mixture of N-(4-(benzo[d][1,3]dioxol-5-ylsulfonyl)benzyl)acetamide (10mg, 0.03 mmol) and 3N HCl (0.36 mL, 1.08 mmol) in 70% i-PrOH (0.2 mL)was heated at 100° C. for 5 hours. The mixture was concentrated todryness to afford the title compound as off-white solid.

¹H NMR (400 MHz, CD₃OD): δ 8.00 (d, J=8.4 Hz, 2H), 7.64 (d, J=8.4 Hz,2H), 7.55(dd, J=8.4 Hz, J′=2 Hz, 1H), 7.34 (d, J=2.4 Hz, 1H), 6.98 (d,J=8 Hz, 1H), 6.08 (s, 2H), 4.19 (s, 2H).

LC-MS: 219.99 (M+1)

d: N-(4-(phenylsulfonyl)benzyl)-1H-pyrrolo[3,2-c]pyridine-2-carboxamide

The title compound was prepared following Example 1C, substituting(4-(benzo[d][1,3]dioxol-5-ylsulfonyl)phenyl)methanamine hydrochloridefor (4-(phenylsulfonyl)phenyl)methanamine, and substituting BOP insteadof HATU. The title compound was purified by PTLC.

¹H NMR (400 MHz, CD₃OD): δ 9.05 (s, 1H), 8.29 (d, J=6 Hz, 1H), 7.90 (d,J=8.4 Hz, 2H), 7.68 (d, J=6 Hz, 1H), 7.57(d, J=8 Hz, 2H), 7.52 (dd,J=8Hz, J′=2 Hz, 1H), 7.42 (s, 1H), 7.31 (d, J=2 Hz, 1H), 6.95 (d, J=8.4Hz, 1H), 6.06 (s, 2H), 4.66 (s, 2H) LC-MS: 435.97 (M+1).

Example 2E1-methyl-N-(4-(phenylsulfonyl)benzyl)-1H-pyrazolo[3,4-b]pyridine-5-carboxamide

Iodomethane (33.5 μL, 0.535 mmol) was added to a mixture ofN-(4-(phenylsulfonyl)benzyl)-1H-pyrazolo[3,4-b]pyridine-5-carboxamide(Example 12; 100 mg, 0.255 mmol) and potassium carbonate (106 mg, 0.764mmol) in DMF (1 mL) at room temperature. The reaction mixture was heatedto 60° C. for 16 hours, whereupon the mixture was diluted with EtOAc andwashed with brine (×3). The organic layer was dried over Na₂SO₄ andconcentrated in vacuo. The residue was dissolved in DMSO (2 mL) andpurified via HPLC to afford the title compound.

¹H NMR (DMSO-d₆): δ 9.31 (t, 1H), 9.02 (d, 1H), 8.72 (d, 1H), 8.28 (s,1H), 7.94-7.90 (m, 4H), 7.66-7.55 (m, 5H), 4.56 (d, 2H), 4.07 (s, 3H).LC-MS: 407.07 (M+1).

Example 2F1-methyl-N-(4-(phenylsulfonyl)benzyl)-1H-pyrrolo[3,2-c]pyridine-2-carboxamide

a: methyl 1-methyl-1H-pyrrolo[3,2-c]pyridine-2-carboxylate

Sodium hydride (48 mg (60%), 1.226 mmol) was added to a ice-coldsolution of 1H-pyrrolo[3,2-c]pyridine-2-carboxylate 9180 mg, 1.022 mmol)in THF (3 mL). The mixture was then warmed to room temperature over 10minutes. Iodomethane (0.070 mL, 1.124 mmol) was added and the mixturestirred for 16 hours. The mixture was partitioned between EtOAc andwater. The combined organic layers were dried over MgSO₄, filtered, andconcentrated to dryness. The residue was purified by Biotage to affordthe title compound.

¹H NMR (CDCl₃): δ 8.90 (s, 1H), 8.35 (d, 1H), 7.92 (s, 1H), 7.20 (d,1H), 3.95 (s, 3H), 3.82 (s, 3H).

b:1-methyl-N-(4-(phenylsulfonyl)benzyl)-1H-pyrrolo[3,2-c]pyridine-2-carboxamide

The title compound was prepared following Example 3C, substitutingmethyl 1-methyl-1H-pyrrolo[3,2-c]pyridine-2-carboxylate and(4-(phenylsulfonyl)phenyl)methanamine for methylthieno[2,3-c]pyridine-2-carboxylate and(4-(4-fluorophenylsulfonyl)phenyl)methanamine, respectively. The titlecompound was purified by PTLC.

¹H NMR (DMSO-D₆): δ 9.27 (t, 1H), 8.91 (s, 1H), 8.28 (d, 1H), 7.92-7.95(m, 4H). 7.53-7.67 (m, 6H), 7.27 (s, 1H), 4.52 (d, 2H), 3.95 (s, 3H).LC-MS: 406.01 (M+1).

Example 2GN-(4-(phenylsulfonyl)benzyl)-1H-imidazo[4,5-c]pyridine-2-carboxamide

a: methyl 1H-imidazo[4,5-c]pyridine-2-carboxylate

Methyl 2,2-dichloro-2-methoxyacetate (1.585 g, 9.16 mmol) was added to asolution of pyridine-3,4-diamine (0.5 g, 4.58 mmol) and DIEA (4.80 mL,27.5 mmol) in DCM (20 mL). The mixture was stirred at room temperaturefor 16 hours, whereupon EtOAc was added and the mixture washed withsaturated sodium bicarbonate and brine. The organic layer was dried overMgSO₄, filtered, concentrated, and purified by Biotage to afford thetitle compound.

¹H NMR (CD₃OD): δ 8.71 (s, 1H), 8.32 (d, 1H), 7.22 (d, 1H), 4.09 (s,3H).

b: N-(4-(phenylsulfonyl)benzyl)-1H-imidazo[4,5-c]pyridine-2-carboxamide

The title compound was prepared following Example 3C, substitutingmethyl 1H-imidazo[4,5-c]pyridine-2-carboxylate and(4-(phenylsulfonyl)phenyl)methanamine for methylthieno[2,3-c]pyridine-2-carboxylate and(4-(4-fluorophenylsulfonyl)phenyl)methanamine, respectively. The titlecompound was purified by PTLC.¹H NMR (CD₃OD): δ 8.32 (s, 1H), 8.16 (d,1H), 7.89-7.93 (m, 4H), 7.51-7.64 (m, 5H), 7.30 (d, 1H), 4.81 (s, 2H).LC-MS: 393.02 (M+1).

Example 2HN-(4-((3-chloro-5-fluorophenyl)sulfonyl)benzyl)furo[2,3-c]pyridine-2-carboxamide

a: ethylfuro[2,3-c]pyridine-2-carboxylate

To a solution of ethyl3-(trifluoromethylsulfonyloxy)furo[2,3-c]pyridine-2-carboxylate (524 mg,1.545 mmol, prepared according to US 20070049603) in ethanol (15 mL) wasadded 10% Pd/C (50 mg) and triethylamine (0.5 mL, 3.59 mmol). Themixture was placed under an atmosphere of hydrogen (balloon) and stirredfor 16 hours. The mixture was filtered, concentrated, and purified bysilica gel chromatography to afford the title compound as an off-whitesolid (278 mg, 94%).

¹H NMR (CDCl₃): δ 9.03 (s, 1H), 8.51 (d, 1H), 7.63 (dd, 1H), 7.52 (d,1H), 4.48 (q, 2H), 1.45 (t, 3H).

MS (ESI): 192.01 (M+H).

b: furo[2,3-c]pyridine-2-carboxylic acid

To a solution of ethyl furo[2,3-c]pyridine-2-carboxylate (3.82 g, 19.98mmol) in water:THF:MeOH (1:1:1, 60 mL) was added potassium hydroxide(3.36 g, 59.9 mmol) and the resulting mixture was stirred at ambienttemperature for 16 hours. The solvent volume was then reduced to ˜20 mLand acetic acid was added until pH ˜4. The solids were collected byvacuum filtration, washed twice with water, and dried in a vacuum ovenovernight to afford the title compound (2.90 g, 89%). ¹H NMR (DMSO-d₆):δ 9.09 (s, 1H), 8.47 (d, 1H), 7.81 (dd, 1H), 7.71 (d, 1H), 3.36 (br s,1H).

c:N-(4-((3-chloro-5-fluorophenyl)sulfonyl)benzyl)furo[2,3-c]pyridine-2-carboxamide

To a mixture of furo[2,3-c]pyridine-2-carboxylic acid (243 mg, 1.487mmol), (4-(3-chloro-5-fluorophenylsulfonyl)phenyl)methanaminehydrochloride (500 mg, 1.487 mmol), and(benzotriazol-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate(724 mg, 1.636 mmol) in DMF (8 mL) was added N,N-diisopropylethylamine(0.571 mL, 3.27 mmol). The homogeneous reaction mixture was stirred for16 hours at ambient temperature, then the DMF was removed under reducedpressure. The residue was treated with EtOAc (10 mL) and 1N NaOH (5 mL)and the mixture was stirred vigorously until a precipitate emerged. Thesolids were collected by vacuum filtration, rinsing with water andEtOAc, to afford the title compound (440 mg, 67%).

¹H NMR (DMSO-d₆): δ 9.62 (t, 1H), 9.03 (s, 1H), 8.46 (d, 1H), 8.02 (dt,2H), 7.87-7.80 (m, 4H), 7.62 (d, 1H), 7.58 (d, 2H), 4.56 (d, 2H).

MS (ESI): 444.82 (M+H).

Example 2IN-(4-(4-(ethylcarbamoyl)phenylsulfonyl)benzyl)imidazo[1,2-a]pyridine-6-carboxamide

a. 4-((4-cyanophenylthio)benzoic acid

In a 250 mL round-bottomed flask was added 4-fluorobenzonitrile (2.121g, 17.51 mmol), 4-mercaptobenzoic acid (3 g, 17.51 mmol), and potassiumcarbonate (7.26 g, 52.5 mmol) in DMF (Volume: 50 mL). The reaction washeated to 100° C. overnight and monitored by LCMS. When complete, theslurry was treated with 100 mL of water to give a clear solution. Thesolution was then treated with 6M aq. HCl slowly until pH<4 upon which aprecipitate formed. The slurry was filtered and washed with water togive 14.8 g of crude product after drying briefly on filter. NMR showedproduct, an impurity and water. Dried in vacuum oven overnight to give4.41 g of material which was adsorbed onto 50 g of silica gel and thenplug filtered with 10% MeOH/CH₂Cl₂ to give 3.45 g of material which wasused without further purification.

¹H NMR (300 MHz, DMSO-d6): δ 13.18 (br s, 1H), 7.96 (d, 2H), 7.80 (d,2H), 7.52 (d, 2H), 7.42 (d, 2H).

b. 4-(4-cyanophenylthio)-N-ethylbenzamide

In a 500 mL round-bottomed flask was added 4-(4-cyanophenylthio)benzoicacid (3.45 g, 13.51 mmol), HBTU (5.13 g, 13.51 mmol) and HOBT (2.070 g,13.51 mmol) in DMF (Volume: 100 mL) followed by ethanamine (2M in THF,20.27 mL, 40.5 mmol). The reaction was stirred overnight and thenconcentrated under reduced pressure. The residue was dissolved in ethylacetate and washed with 2M aq. NaOH, water and brine. The organic layerwas separated, dried with anhydrous sodium sulfate, filtered andconcentrated to give 2.81 g of product. Material used without furtherpurification.

¹H NMR (300 MHz, DMSO-d6): δ 8.57 (t, 1H), 7.89 (d, 2H), 7.75 (d, 2H),7.55 (d, 2H), 7.31 (d, 2H), 3.30 (m, 2H), 1.10 (t, 3H).

c. 4-(4-cyanophenylsulfonyl)-N-ethylbenzamide

In a 500 mL round-bottomed flask was added4-(4-cyanophenylthio)-N-ethylbenzamide (2.81 g, 9.95 mmol) in chloroform(Volume: 50 mL) which was cooled to 0° C. followed by the addition ofmCPBA (6.87 g, 29.9 mmol). The reaction was stirred for 1 hour at 0° C.and then warmed to room temperature overnight. The reaction was dilutedwith chloroform and poured into a separatory funnel. The organic layerwas washed with 10% aqueous sodium thiolsulfate, 2M NaOH, and saturated,aqueous sodium chloride. The bottom was separated, dried with anhydroussodium sulfate, filtered and concentrated under reduced pressure to give2.79 g of crude product. Material purified on Biotage to give 2.42 g ofpure product (70% yield).

¹H NMR (300 MHz, DMSO-d6): δ 8.68 (t, 1H), 8.15 (d, 2H), 8.09 (m, 4H),7.95 (d, 2H), 3.28 (m, 2H), 1.02 (t, 3H).

LC-MS (ESI): 314.92 (M+1).

d. 4-(4-(aminomethyl)phenylsulfonyl)-N-ethylbenzamide

A slurry of Raney Nickel (0.660 g, 7.70 mmol) was added to a Paar flaskand washed with methanol. The MeOH was removed by pipette and theprocess repeated twice more. 4-(4-cyanophenylsulfonyl)-N-ethylbenzamide(2.42 g, 7.70 mmol) in MeOH (Volume: 50 mL)) was then added followed bypotassium hydroxide (0.043 g, 0.770 mmol) and ammonia (7M, 11.00 mL, 77mmol) in MeOH. The slurry was placed on the Paar shaker and hydrogenatedat 35 psi overnight. Reaction monitored by LCMS. The solution was thenfiltered through celite and washed with MeOH. The solution was thenconcentrated under reduced pressure to give 2.56 g of product. Materialpurified on Biotage to give 2.03 g of product (83% yield).

¹H NMR (300 MHz, DMSO-d6): δ 8.65 (t, 1H), 7.98 (m, 4H), 7.88 (d, 2H),7.55 (d, 2H), 3.76 (d, 2H), 3.24 (m, 2H), 2.10 (br s, 2H), 1.15 (t, 3H).

LC-MS (ESI): 318.95 (M+1).

e.N-(4-(4-(ethylcarbamoyl)phenylsulfonyl)benzyl)imidazo[1,2-a]pyridine-6-carboxamide

In a 250 mL round-bottomed flask was added4-(4-(aminomethyl)phenylsulfonyl)-N-ethylbenzamide (1 g, 3.14 mmol),imidazo[1,2-a]pyridine-6-carboxylic acid (0.509 g, 3.14 mmol) and HATU(1.314 g, 3.45 mmol) in DMF (Volume: 50 mL) followed by DIEA (1.207 mL,6.91 mmol). The reaction was stirred overnight and then concentratedunder reduced pressure. The reaction was diluted with methylene chlorideand poured into a separatory funnel. The organic layer was washed with1M NaOH and water. The bottom was separated and concentrated andpurified directly on the Biotage to give 514mg of clean product (35%yield).

¹H NMR (300 MHz, DMSO-d6): δ 9.19 (t, 1H), 9.11 (t, 1H), 8.64 (t, 1H),8.04-9.92 (m, 7H), 6.63 (m, 3H), 7.55 (d, 2H), 4.53 (d, 2H), 3.25 (m,2H), 1.08 (t, 3H).

LC-MS (ESI): 463.05 (M+1).

Example 2JN-(4-((3-methoxyphenyl)sulfonyl)benzyl)imidazo[1,2-a[pyrimidine-6-carboxamide

The title compound was prepared with 80% yield by following Example 4D.

¹H NMR δ (d₆-dmso) 9.47 (1H, d); 9.34 (1H, t); 8.92 (1H, d); 8.01 (1H,d); 7.95 (2H, d); 7.80 (1H, d); 7.58 (2H, d); 7.54-7.47 (2H, m);7.42-7.41 (1H, m); 7.23 (1H, dt); 4.57 (2H, d and 3.81 (3H, s).

LC-MS (ESI): 422.9 (M+1).

Example 2K N-(4-(1-isopropyl-1H-pyrazol-4-ylsulfonyl)benzyl)imidazo [1,2-a]pyridine-6-carboxamide

a. N-(4((1-isopropyl-1H-Pyrazol-4-yl) sulfonyl) benzyl) acetamide

In a 1 L round-bottomed flask were added sodium4-(acetamidomethyl)benzenesulfinate (3.97 g, 16.89 mmol, 1.3 eq.),1-isoproyl 1H-pyrazol-4-ylboronic acid(2 g, 12.99 mmol)] and COPPER (II)ACETATE (2.6 g, 14.29 mmol)), POTASSIUM CARBONATE (3.95 g, 28.6 mmol) inDMSO (50 ml) followed by 10 g of 4 Å molecular sieves. The reaction wasstirred overnight. Added water and EtOAc, filtered through a shortcelite pad, added EtOAc, washed with water twice, dried andconcentrated. The biotage column purification afforded 1.9 g ofN-(4-((1-isopropyl-1H-Pyrazol-4-yl) sulfonyl)benzyl)acetamide (45%).

¹HNMR (DMSO-D₆): δ 8.50(s, 1H). 8.42 (t, 1H), 7.91 (s, 1H), 7.86 (d,2H), 7.43 (d, 2H), 4.52(m, 1H), 4.28(d, 2H), 1.36(d, 6H)

b. (4-(1-isopropyl-1H-pyrazol-4-ylsulfonyl)phenyl)methanamine HCl

The mixture of a 3M HCl solution(80 ml) and,N-(4-(1-isopropyl-1H-pyrazol-4-ylsulfonyl)benzyl)acetamide (1.9 g, 5.91mmol) in 2-Propanol (100 ml) was refluxed for over weekend, removedsolvent, added ether, filtered and dried to afford 1.4 g of(4-(1-isopropyl-1H-pyrazol-4-ylsulfonyl)phenyl)methanamine HCl salt(75%)

¹HNMR (DMSO-d₆): δ 8.50 (s, 1H), 7.94-7.98 (m, 3H), 7.85 (dd, 1H), 7.69(d, 2H), 4.52(m, 1H), 4.08(d, 2H), 1.37(d, 6H).

c. N-(4-(1-isopropyl-1H-pyrazol-4-ylsulfonyl) benzyl) imidazo [1,2-a]pyridine-6-carboxamide

In a 250 mL round-bottomed flask were addedimidazo[1,2-a]pyridine-6-carboxylic acid (0.719 g, 4.43 mmol),(4-(1-isopropyl-1H-pyrazol-4-ylsulfonyl)phenyl)methanamine, HCl (1.4 g ,4.43 mmol) and HBTU (1.849 g, 4.88 mmol), HOBT (0.747 g, 4.88 mmol) andDIEA (3.87 mL, 22.16 mmol) in DMF (Volume: 50 mL). The reaction wasstirred overnight and then concentrated under reduced pressure. Theresidue was diluted with methylene chloride and washed with 1M aq. NaOH.The organic layer was separated and concentrated and directly purifiedin the Biotage to give 1.24 g ofN-(4-(1-isopropyl-1H-pyrazol-4-ylsulfonyl)benzyl)imidazo[1,2-a]pyridine-6-carboxamide.

¹HNMR (DMSO-D₆): δ 9.20 (t, 1H), 9.13(s, 2H), 8.51 (s, 1H), 8.05 (s,1H), 7.88-7.91 (m, 3H), 7.53-7.67 (m, 4H), 4.42-4.55 (m, 3H), 1.37 (d,6H).

LC-MS: 424.01 (M+1)

Example 2LN-(4-(phenylsulfonyl)benzyl)-1H-pyrazolo[3,4-b]pyridine-5-carboxamide

The mixture of 1H-pyrazolo[3,4-b]pyridine-5-carboxylic acid (0.8 g, 4.90mmol), HATU (1.87 g, 4.90 mmol), diisopropylethylamine (1.2 mL, 6.69mmol), and (4-(phenylsulfonyl)phenyl)methanamine (1.10 g, 4.46 mmol) inDMF (50 mL) was stirred at room temperature for 16 h. The DMF wasremoved under reduced pressure. 150 mL of water was added to the residueand extracted with EtOAc (3×100 mL). The combined organic layers waswashed with water, saturated sodium bicarbonate, brine, dried withsodium sulfate, and concentrated in vacuo. The crude was purified byBiotage with MeOH/DCM (0%-10%) to yield the title compound.

¹H NMR (DMSO-d6): δ 9.27 (t, 1H), 8.98 (d, 1H), 8.72 (d, 1H), 8.27 (s,1H), 7.94-7.90 (m, 4H), 7.66-7.55 (m, 5H), 4.56 (d, 2H).

LC-MS: 393.01 (M+1).

Example 2MN-(4-(2,4-dimethylthiazol-5-ylsulfonyl)benzyl)imidazo[1,2-a]pyridine-6-carboxamide

A mixture of copper iodide (0.2 M DMSO, 100 μL, 20 μmol), cesium(S)-pyrrolidine-2-carboxylate (0.2 M DMSO w/14% MeOH (v/v), 200 μL, 40μmol), sodium 4-(acetamidomethyl)benzenesulfinate (0.2 M DMSO, 200 μL,40 μmol) and 5-bromo-2,4-dimethylthiazole (0.2 M DMSO, 240 μL, 48 μmol)was heated at 90° C. with shaking over night. The reaction was treatedwith aqueous ammonia and extracted with EtOAc and the organic extractwas concentrated to dryness and the resulting residue was dissolved in70% i-PrOH (0.35 mL) and 3N HCl (0.35 mL, 1.05 mmol) and was heated at90° C. for 4 hours then concentrated to dryness. The residue was treatedwith triethylamine (5% in ACN (v/v), 200 uL) andimidazo[1,2-a]pyridine-6-carboxylic acid (0.2 M in DMA w/10% TEA (v/v),240 uL, 48 umol) and BOP (0.2 M DCE, 260 uL, 52 umol). The solution washeated to 40° C. for 4 h then cooled to room temperature and partitionedbetween NaOH and EtOAc. The organic layer was separated and concentratedin vacuo. The crude was purified by LC/MS to afford the title compoundas white solid.

¹H NMR (400 MHz, CDCl₃): δ 8.87 (dd, J=1.6 Hz, J′=0.8 Hz 1H), 7.89 (dt,J=8.4 Hz, J′=2 Hz, 2H), 7.71 (d, J=1.6 Hz, 1H), 7.67 (s, 1H), 7.60 (d,J=9.2 Hz, 1H), 7.50 (d, J=8.4 Hz 2H), 7.43 (dd, J=9.2 Hz, J′=2 Hz, 1H),6.84 (bs, 1H), 4.73 (d, J=6 Hz, 2H), 2.65 (s, 3H), 2.57 (s, 3H).

LC-MS: 427.10 (M+1)

Example 2NN-(3-(naphthalen-2-ylsulfonyl)benzyl)imidazo[1,2-a]pyridine-6-carboxamide

To a mixture of sodium 4-(acetamidomethyl)benzenesulfinate (0.2 M MeOH,100 μL, 20 μmol) and zinc chloride (0.5 M THF, 40 μL, 20 μmol), cesiumcarbonate (1.43 M MeOH, 25 μL, 35 μmol) then 2-bromonapthelene (0.2 MToluene, 110 μL, 22 μmol) were added. A toluene solution of XantPhos andPd₂dba₃ (0.01 M XantPhos/0.005 M Pd₂dba₃, 50 μL, 2.5 mol %) was addedand the reaction was heated for 4 h at 95° C. under nitrogen. Thereaction was cooled to room temperature and 70% i-PrOH (0.35 mL) and 3NHCl (0.35 mL, 1.05 mmol) were added and was heated at 95° C. for 4 hoursthen concentrated to dryness. The residue was treated with triethylamine(5% in ACN (v/v), 100 μL) and imidazo[1,2-a]pyridine-6-carboxylic acid(0.2 M in DMA w/10% TEA (v/v), 120 μL, 24 μmol) and BOP (0.2 M DCE, 130μL, 26 μmol). The solution was heated to 40° C. for 4 h then cooled toroom temperature and partitioned between NaOH and EtOAc. The organiclayer was separated and deposited on a SCX-SPE cartridge which waseluted to two fractions: the 1^(st) with 25% McOH/EtOAc (v/v), the2^(nd) with Et3N/MeOH/EtOAc (1:1:10 v/v/v). The second fraction wasconcentrated to dryness and was purified by LC/MS to afford the titlecompound as white solid.

¹H NMR (400 MHz, CDCl₃): δ 8.85 (s, 1H), 8.55 (s, 1H), 7.93 (m, 4H),7.87 (d, J=8 Hz, 1H), 7.81 (dd, J=8.8 Hz, J′=1.6 Hz, 1H), 7.63 (m, 5H),7.47 (d, J=8.4 Hz, 2H), 7.34 (m, 1H), 6.81 (m, 1H), 4.70 (d, J=5.6 Hz,2H).

LC-MS: 442.13 (M+1)

Example 2ON-(4-(naphthalen-2-ylsulfonyl)benzyl)furo[2,3-c]pyridine-2-carboxamide

a. tert-butyl 4-bromobenzylcarbamate

A 200-mL RBF equipped with a magnetic stir bar was charged with(4-bromophenyl)methanamine hydrochloride (5.23 g, 23.50 mmol), K₂CO₃(3.90 g, 28.2 mmol), MeTHF (Ratio: 4.00, Volume: 50 ml), and Water(Ratio: 1.000, Volume: 12.5 ml). To the resulting mixture was addedBOC₂O (6.00 ml, 25.9 mmol) in one portion at rt with stirring. LCMSafter 1 h suggested clean, complete conversion. The mixture was dilutedwith additional MeTHF (50 mL) and water (10 mL), and the layersseparated. The organic layer was washed with half-saturated brine (2×25mL) and then concentrated under reduced pressure to 7.2 g of a whitesolid. The crude product was used without further purification in thenext step.

¹H NMR (400 MHz, CDCl₃): δ 7.44 (d, J=8.4 Hz, 2H), 7.15 (d, J=8.3 Hz,2H), 4.85 (br s, 1H), 4.26 (d, J=5.8 Hz, 2H), 1.45 (s, 9H) ppm.

b. methyl 3-(4-((tert-butoxycarbonylamino)methyl)phenylthio)propanoate

A 200-mL RBF equipped with a magnetic stir bar and containing tert-butyl4-bromobenzylcarbamate, crude (6.72 g, 23.5 mmol) was charged withToluene (Volume: 50 ml), Hunig'sBase (8.21 ml, 47.0 mmol), XANTPHOS(0.680 g, 1.175 mmol), Pd₂(dba)₃ (0.538 g, 0.588 mmol), and finallymethyl 3-mercaptopropanoate (2.60 ml, 23.50 mmol). The mixture was thenheated to 100° C. LCMS after 1 h suggested significant conversion,although starting bromide was still evident by 220 nm. LCMS after 2 h alittle better. After 2.5 h, heating was discontinued. After cooling, themixture was loaded directly on a short silica gel column. Elution with5:1 hexanes-EtOAc, 4:1 hexanes-EtOAc, and finally 3:1 hexanes-EtOAcafforded methyl3-(4-((tert-butoxycarbonylamino)methyl)phenylthio)propanoate (7.19 g,22.09 mmol, 94% yield) as a nearly colorless oil.

¹H NMR (400 MHz, CDCl₃): δ 7.32 (d, J=8.3 Hz, 2H), 7.21 (d, J=8.2 Hz,2H), 4.84 (br s, 1H), 4.28 (d, J=5.8 Hz, 2H), 3.67 (s, 3H), 3.14 (t,J=7.4 Hz, 2H), 2.61 (t, J=7.5 Hz, 2H), 1.45 (s, 9H) ppm.

ESMS: 348.15 (M+Na)

c. methyl3-(4-((tert-butoxycarbonylamino)methyl)phenylsulfonyl)propanoate

A 500-mL RBF equipped with a magnetic stir bar was charged with OXONE(23.61 g, 38.4 mmol) and Water (Ratio: 1.822, Volume: 82 ml). Themixture was stirred at rt for 5 min in order to dissolve the Oxone.Next, a solution of methyl3-(4-((tert-butoxycarbonylamino)methyl)phenylthio)propanoate (5.0 g,15.36 mmol) in Acetonitrile (Ratio: 1.000, Volume: 45 ml) was added atrt with rapid stirring. The mixture was stirred at rt. After 2.5 h, analiquot was removed, worked up, and analyzed by ¹H NMR, which confirmedcomplete conversion to sulfone. LCMS also looked good. The reactionmixture was then extracted with EtOAc (100 mL). This extract wasconcentrated under reduced pressure. The aqueous layer was re-extractedonce with fresh EtOAc. This extract was combined with the first,concentrated extract. The combined solution was washed twice withhalf-saturated brine (2 x 50 mL) and concentrated under reduced pressureto afford methyl3-(4-((tert-butoxycarbonylamino)methyl)phenylsulfonyl)propanoate (5.17g, 14.46 mmol, 94% yield) as a white solid.

¹H NMR (400 MHz, CDCl₃): δ 7.86 (d, J=8.4 Hz, 2H), 7.48 (d, J=8.6 Hz,2H), 5.03 (br s, 1H), 4.41 (d, J=6.2 Hz, 2H), 3.64 (s, 3H), 3.41 (t,J=7.7 Hz, 2H), 2.74 (t, J=7.8 Hz, 2H), 1.46 (s, 9H) ppm.

ESMS: 380.07 (M+Na)

d. methyl 3-(4-(aminomethyl)phenylsulfonyl)propanoate hydrochlorid

A 200-mL RBF equipped with a magnetic stir bar and containing methyl3-(4-((tert-butoxycarbonylamino)methyl)phenylsulfonyl)propanoate (5.16g, 14.44 mmol) was charged with MeOH (Volume: 50 ml) followed byHYDROCHLORIC ACID, cone (1.323 ml, 15.88 mmol). The solution was thenheated to 50° C. LCMS after overnight indicated complete conversion.Heating was discontinued. After cooling, the slurry was concentratedpartially under reduced pressure, removing 32 mL of MeOH. The resultingconcentrated slurry was diluted with MTBE (50 mL). The slurry wasstirred at rt for 30 min, then filtered on a glass, medium frit, 60-mLBuchner funnel. The filter cake was washed with MTBE and dried undersuction and a positive pressure of nitrogen to afford methyl3-(4-(aminomethyl)phenylsulfonyl)propanoate hydrochloride (4.10 g, 13.96mmol, 97% yield) as a snow-white, crystalline, free-flowing solid.

¹H NMR (400 MHz, DMSO-d₆): δ 8.62 (br s, 2H), 7.92 (d, J=8.5 Hz, 2H),7.77 (d, J=8.4 Hz, 2H), 4.14 (s, 2H), 3.58 (t, J=7.3 Hz, 2H), 3.52 (s,3H), 2.59 (t, J=7.3 Hz, 2H) ppm.

ESMS: 258.10 (M+1).

e. methyl3-(4-((furo[2,3-c]pyridine-2-carboxamido)methyl)phenylsulfonyl)propanoate

A 25-mL RBF equipped with a magnetic stir bar was charged withfuro[2,3-c]pyridine-2-carboxylic acid (135 mg, 0.828 mmol), methyl3-(4-(aminomethyl)phenylsulfonyl)propanoate hydrochloride (243 mg, 0.828mmol), EtOH (Volume: 2.7 ml), N-METHYLMORPHOLINE (0.218 ml, 1.986 mmol),and finally EDC (190 mg, 0.993 mmol). The reaction mixture was stirredat rt. LCMS after 75 min shows some conversion, with longer-retainingby-product also forming. LCMS after 3 h shows some more conversion, butnot significant. After 3.5 h, HOBT (6.34 mg, 0.041 mmol) was added.LCMS, 75 min after HOBT addition, not much different. LCMS afterovernight not much different. The reaction mixture was slowly dilutedwith water (8.1 mL). The resulting slurry was stirred at rt for 1 h,then filtered on a 30-mL, medium frit, glass Buchner funnel. The solidwas washed with water and dried under suction and a positive pressure ofnitrogen to yield methyl3-(4-((furo[2,3-c]pyridine-2-carboxamido)methyl)phenylsulfonyl)propanoate(0.12 g, 0.298 mmol, 36.0% yield) as a slightly off-white fluffy powder.

¹H NMR (400 MHz, DMSO-d₆): δ 9.67 (t, J=6.1 Hz, 1H), 9.05 (s, 1H), 8.47(d, J=5.2 Hz, 1H), 7.85 (d, J=8.4 Hz, 2H), 7.82 (dd, J=5.3, 1.1 Hz, 1H),7.65 (d, J=0.8 Hz, 1H), 7.60 (d, J=8.4 Hz, 2H), 4.59 (d, J=6.1 Hz, 2H),3.53 (t, J=7.2 Hz, 2H), 3.49 (s, 3H), 2.59 (t, J=7.2 Hz, 2H) ppm.

ESMS: 403.03 (M+1)

f. sodium 4-((furo[2,3-c]pyridine-2-carboxamido)methyl)benzenesulfinate

A 25-mL RBF equipped with a magnetic stir bar was charged with methyl3-(4-((furo[2,3-c]pyridine-2-carboxamido)methyl)phenylsulfonyl)propanoate(113 mg, 0.281 mmol) followed by a solution of SODIUM ETHOXIDE (21wt %in EtOH) (91 mg, 0.281 mmol) dissolved in MeOH (Volume: 2 ml). Themixture was stirred at rt. Over time, the solid dissolved. LCMS after 30min shows ca 80-85% conversion. LCMS after 1 h shows essentiallycomplete conversion. Note: no transient intermediate/by-product isomericwith the SM was observed as in the case with the analogous azaindoleexperiments. LCMS after 2 h shows complete, clean conversion. After 2.5h, the solution was concentrated under a gentle stream of nitrogenovernight to afford sodium4-((furo[2,3-c]pyridine-2-carboxamido)methyl)benzenesulfinate (0.102 g,0.301 mmol, 107% yield) as an off-white/light tan solid.

¹H NMR (400 MHz, DMSO-d₆): δ 8.99 (s, 1H), 8.42 (d, J=5.2 Hz, 1H), 7.76(dd, J=5.2, 1.1 Hz, 1H), 7.55 (d, J=0.6 Hz, 1H), 7.38 (d, J=8.0 Hz, 2H),7.25 (d, J=8.1 Hz, 2H), 4.44 (s, 2H) ppm.

ESMS: 317.04 (M+1)

g.N-(4-(naphthalen-2-ylsulfonyl)benzyl)furo[2,3-c]pyridine-2-carboxamide

To a mixture of naphthylen-2-boronic acid (0.2 M dioxane, 150 μL, 30μmol) and diacetoxycopper (0.2 M DMSO, 150 μL, 30 μmol) andtriethylamine (Neat, 9.3 μL, 67 μmol),sodium4-((furo[2,3-c]pyridine-2-carboxamido)methyl) benzene sulfinate (0.2 MDMSO, 50 μL, 10 μmol) was added and the reaction was heated at 40° C.over night. The reaction was cooled to room temperature and partitionedbetween aqueous ammonia and EtOAc. The organic layer was separated anddeposited on a SCX-SPE cartridge which was eluted to two fractions: the1^(st) with 25% MeOH/EtOAc (v/v), the 2^(nd) with ammonia in methanol (2N). The second fraction was concentrated to dryness and was purified byLC/MS to afford the title compound as white solid.

¹H NMR (400 MHz, CDCl₃): δ 8.89 (s, 1H), 8.56 (d, J=2 Hz, 1H), 8.50 (d,J=5.2 Hz, 1H), 7.99 (m, 3H), 7.92 (d, J=8.8 Hz, 1H), 7.87 (m, 2H), 7.62(m, 3H), 7.51 (m, 3H), 7.08 (m, 1H), 4.72 (d, J=6.4 Hz, 2H).

LC-MS: 443.22 (M+1)

Example 2P N-(4-(5-(dimethylamino) pyrazin-2-ylsulfonyl) benzyl) imidazo[1, 2-a]pyridine-6-carboxamide

a. N-(4-(5-(dimethylamino)pyrazin-2-ylsulfonyl)benzyl) acetamide

The mixture of XANTPHOS (0.573 g, 0.990 mmol), Cs2CO3 (6.45 g, 19.80mmol), Pd2(dba)3 (0.453 g, 0.495mmol),4-(acetamidomethyl)benzenesulfinic acid, sodium salt (3.51 g,14.85 mmol), 5-bromo-N,N-dimethylpyrazin-2-amine (2 g, 9.90 mmol) inToluene (50 ml) was degassed and heated to 120° C. for overnight. Cooledto RT, added EtOAc, washed with water, dried and concentrated, TheBiotage purification afforded 1.6 g of the target compound (48%).

¹HNMR (CDCl₃): δ 8.75(s, 1H). 8.03 (s, 1H), 7.87 (d, 2H), 7.38 (d, 2H),6.11 (b, 1H), 4.45 (d, 2H), 3.21 (s, 6H), 2.16 (s, 3H).

b. 5-((4-(aminomethyl)phenyl)sulfonyl)-N,N-dimethylpyrazin-2-aminehydrochloride:

The mixture of a 3M HCl solution(80 ml) and,N-(4-(5-(dimethylamino)pyrazin-2-ylsulfonyl)benzyl)acetamide(1.6 g) in2-Propanol (100 ml) was refluxed for over weekend, removed solvent,added ether, filtered and dried to afford 1.2 g of the target compoundas a hydrochloride (76%).

¹HNMR (DMSO-D₆): δ 8.71 (s, 1H), 8.14 (s, 1H), 7.92 (d, 2H), 7.45 (d,2H), 4.08(d, 2H), 3.13(s, 6H).

c. N-(4-(5-(dimethylamino) pyrazin-2-ylsulfonyl) benzyl) imidazo f 1,2-a]pyridine-6-carboxamide

In a 250 mL round-bottomed flask was addedimidazo[1,2-a]pyridine-6-carboxylic acid (0.592 g, 3.65 mmol),5-(4-(aminomethyl)phenylsulfonyl)-N,N-dimethylpyrazin-2-amine, HCl (1.2g, 3.65 mmol) and HBTU (1.522 g, 4.01 mmol), HOST (0.615 g, 4.01 mmol)and DIEA (3.19 mL, 18.25 mmol) in DMF (50 mL). The reaction was stirredovernight and then concentrated under reduced pressure. The residue wasdiluted with methylene chloride and washed with 1M aq. NaOH. The organiclayer was separated and concentrated and directly purified in theBiotage to give 235 mg of N-(4-(5-(dimethylamino) pyrazin-2-ylsulfonyl)benzyl)imidazo[1,2-a]pyridine-6-carboxamide (15%).

¹HNMR (DMSO-d₆): δ 9.21 (t, 1H), 9.13 (s, 1H), 8.67 (s, 1H), 8.12 (s,1H), 8.95 (s, 1H), 7.86 (d, 2H), 7.63 (d, 2H), 7.54 (d, 2H), 4.53 (d,2H), 3.11 (s, 6H).

LC-MS: 437.0 (M+1)

Example 2Q N-(4-((3-(trifluoromethoxy)phenyl)sulfonyl)benzyl)imidazo[1,2-a]pyrimidine-6-carboxamide

a: 4-((3-(trifluoromethoxy)phenyl)thio)benzonitrile

To a colorless solution of 3-(trifluoromethoxy)benzenethiol (5.0 g, 25.8mmol) in DMF (80 mL) was added K₂CO₃ (4.21 g, 30.4 mmol) forming ayellow mixture. To this mixture was added 4-fluorobenzonitrile (2.84 g,23.4 mmol). The mixture was heated to 120° C. for 16 h, cooled to roomtemperature, and diluted with 1N NaOH and Et2O. The layers wereseparated. The organic layer was washed sequentially with 1N NaOH andbrine, dried over Na₂SO₄, and concentrated in vacuo. The residue waspurified by Biotage SP1 to afford the desired product as colorless oil(6.09 g, 88% yield).

¹H NMR (300 MHz, CDCl₃): δ 8.8-8.06 (m, 2H), 7.89-7.80 (m, 2H),7.78-7.82 (m, 2H), 7.61 (t, 1H), 7.47 (d, 2H).

LC-MS: 295.93 (M+H).

b: 4-((3-(trifluoromethoxy)phenyl)sulfonyl)benzonitrile

To a solution of 4-(3-(trifluoromethoxy)phenylthio)benzonitrile (6.09 g,20.6 mmol) in CHCl₃ (110 mL) at 0° C. was added mCPBA (20.88 g, 91.0mmol). The mixture was stirred and warmed to room temperature slowlyovernight. The solids were removed by vacuum filtration, rinsed withCHCl₃. The filtrate was washed with 1N NaOH (×2). The separated organiclayer was washed with water and brine, dried over Na₂SO₄, filtered,concentrated to afford the product without further purification for nextstep (6.00 g, 89%).

¹H NMR (300 MHz, CDCl₃): δ 8.08 (d, 1H), 8.06 (d, 1H), 7.89-7.80 (m,4H), 7.61 (t, 1H), 7.49-7.43 (m, 1H).

LC-MS: 349.90 (M+Na).

c: (4((3-(trifluoromethoxy)phenyl)sulfonyl)phenyl)methanamine

To a small flask was added 3 pipette-full slurry of Raney Ni in waterand then added methanol (2 mL). The wash solvent (MeOH) was removed viapipette. The wash was repeated twice more, affording about 7 equivalentsof nickel. To a 500 mL Parr reaction cylinder was added4-(3-(trifluoromethoxy)phenylsulfonyl)benzonitrile (6.00 g, 18.3 mmol)in MeOH (120 ml), followed by addition of the prewashed nickel, 7Nammonia (37.2 ml, 26.0 mmol) in MeOH and potassium hydroxide (0.329 g,5.9 mmol). The mixture was vacuumed and purged with H₂ three times, thenhydrogenated at 50 psi overnight. LC-MS analysis indicated thecompletion of the hydrogenation of nitrile. The mixture was filteredthrough celite. The filtrate was concentrated and purified by BiotageSP1 affording the product as light yellow oil (4.20 g, 93% yield).

¹H NMR (300 MHz, DMSO-d₆): δ 7.99-7.91 (m, 4H), 7.75-7.73 (m, 3H), 7.58(d, 2H), 3.76 (s, 2H).

LC-MS: 331.97 (M+H).

d:N-(4-((3-(trifluoromethoxy)phenyl)sulfonyl)benzyl)imidazo[1,2-a]pyrimidine-6-carboxamide

A mixture of imidazo[1,2-a]pyrimidine-6-carboxylic acid (0.739 g, 4.53mmol), (4-(3-(trifluoromethoxy)phenylsulfonyl)phenyl)methanamine (1.5 g,4.53 mmol), BOP (2.203 g, 4.98 mmol) and DIEA (0.949 mL, 5.43 mmol) inDMF (25 mL) was stirred at room temperature overnight. The reactionmixture was concentrated in vacuo to remove the DMF. The residue wasdiluted with EtOAc and then washed with 1N NaOH. The separated aqueouslayer was back-extracted with EtOAc. The combined organic extracts werewashed with 5% AcOH, water, brine and dried (Na₂SO₄), filtered andconcentrated. Purification by Biotage SP1 of the crude afforded thetitle compound as off-white solids (980 mg, 45% yield).

¹H NMR (300 MHz, DMSO-d₆): δ 9.47(d, 1H), 9.35(t, 1H), 9.23(d, 1H),8.01-7.98(m, 5H), 7.80-7.31(m, 3H), 7.60(d, 2H), 4.57 (d, 2H).

LC-MS: 476.87 (M+1).

Example 2RN-(4-(benzylsulfonyl)benzyl)-1H-pyrrolo[3,2-c]pyridine-2-carboxamide

a: N-(4-(benzylsulfonyl)benzyl)acetamide

To a solution of sodium 4-(acetamidomethyl)benzenesulfinate (1 g, 4.25mmol) in water (12 mL) were added TBAI (0.157 g, 0.425 mmol) and(bromomethyl)benzene (0.742 g, 4.34 mmol) under N₂ flow. The reactionmixture was heated to 70° C. for 2h. The white solids were precipitatedout. LC-MS analysis showed that the major peak was the desired product.The white solids were filtered and washed with water and ether to removeTBAI, then dried under reduced pressure to give 696 mg of desiredproduct with 90% HPLC purity. The collected solids were used for nextstep without further purification.

-   -   ¹H NMR (300 MHz, CDCl₃): δ 7.55 (d, 2H), 7.33-7.23 (m, 5H), 7.08        (d, 2H), 5.94 (brs, 1H), 4.50 (d, 2H), 4.29 (s, 2H), 2.07 (s,        3H).

LC-MS: 304.12 (M+H).

b: (4-(benzylsulfonyl)phenyl)methanamine hydrochloride

A mixture of N-(4-(benzylsulfonyl)benzyl)acetamide (300 mg, 0.989 mmol)and 3N HCl (11.87 ml, 35.6 mmol) in ^(i)PrOH (11 mL) was heated to 100°C. The cloudy mixture turned to a clear solution as temperature rose.The reaction mixture was stirred for 16 h at 100° C. LC-MS analysisindicated completion of hydrolysis. The reaction mixture was allowed tocool to room temperature. The white crystals were precipitated andfiltered, rinsed with cold mixture of ^(i)PrOH/ether to affordhydrochloride salt of the desired product (235 mg, 80% yield).

¹H NMR (300 MHz, DMSO-d₆): δ 8.44 (brs, 3H), 7.75, 7.65 (dd, 4H),7.29-7.27 (m, 3H), 7.16-7.13 (m, 2H), 4.69 (s, 2H), 4.12 (s, 2H).

LC-MS : 262.11(M+H).

c: N-(4-(benzylsulfonyl)benzyl)-1H-pyrrolo[3,2-c]pyridine-2-carboxamide

1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid (57.2 mg, 0.353 mmol),1H-benzo[d][1,2,3]triazol-1-ol (59.0 mg, 0.437 mmol) and EDC (86 mg,0.450 mmol) were dissolved in anhydrous THF (4 mL), followed by additionof Hunig's base (0.12 mL, 0.7 mmol). The mixture formed a slurrysolution. DMF (1 mL) was added. After stirring for 15 min.,(4-(benzylsulfonyl) phenyl)methanamine hydrochloride (100 mg, 0.336mmol) and Hunig's base (0.12 mL, 0.7 mmol) in THF (1 mL) was added. Thereaction mixture was heated and stirred at 65° C. overnight, thendiluted with ethyl acetate (×2). The combined organic layers were washedsequentially with 5% aqueous acetic acid (xl), saturated aqueous sodiumbicarbonate (×2), and brine (×1). The organic layer was dried overanhydrous sodium sulfate, filtered and concentrated in vacuo to yield acrude product (65 mg). The crude was dissolved in DCM and a few drops ofMeOH, and purified by Biotage to give the desired product (34 mg, 25%yield).

¹H NMR (300 MHz, DMSO-d₆): δ 12.05 (s, 1H), 9.31 (t, 1H), 8.93 (s, 1H),8.21 (d, 1H), 7.68 (d, 2H), 7.51(d, 2H), 7.36-7.26 (m, 5H), 7.16-7.13(m, 2H), 4.63 (s, 2H), 4.59 (d, 2H).

LC-MS: 406.11(M+H).

Example 2SN-(4-(cyclohexylsulfonyl)benzyl)-1H-pyrrolo[3,2-c]pyridine-2-carboxamide

a: N-(4-(cyclohexylsulfonyl)benzyl)acetamide

To a solution of sodium 4-(acetamidomethyl)benzenesulfinate (500 mg,2.126 mmol) in DMSO (8 mL) was added iodocyclohexane (670 mg, 3.19mmol). The reaction was heated up to 100° C. for 48 h. The reactionmixture was diluted with EtOAc, and washed with water (×1) and brine(×2). The organic was dried over Na₂SO₄ and concentrated. The crude waspurified by Biotage to yield the desired product (52 mg, 8% yield).

¹H NMR (300 MHz, CDCl₃): δ 7.66 (d, 2H), 7.36 (d, 2H), 6.72 (m, 1H),4.46 (d, 2H), 2.83 (tt, 1H), 2.04 (s, 3H), 2.01-2.00 (m, 2H), 1.83-1.76(m, 3H), 1.65 (d, 1H), 1.93-1.12 (m, 4H).

LC-MS: 296.06 (M+H).

b: (4-(cyclohexylsulfonyl)phenyl)methanamine

A mixture of N-(4-(cyclohexylsulfonyl)benzyl)acetamide (52 mg, 0.176mmol) and 3N HCl (2.11 mL, 6.34 mmol) in ^(i)PrOH (2.5 mL) was heated to100° C. The cloudy mixture turned to a clear solution as temperaturerose. The reaction mixture was stirred and refluxed for 16 h at 100° C.LC-MS analysis indicated that no starting material was present and someother by-product was formed (the desired product showed as 22% in HPLC).The mixture was cooled to RT and the solvent was concentrated. Theresulting slurry was treated with 1N NaOH and EtOAc. The combinedorganic extracts were washed with brine, dried and concentrated to yielda crude product (120 mg). The crude was purified by Biotage to yield thefree amine (25 mg, 56% yield).

LC-MS: 254.08 (M+H).

c:N-(4-(cyclohexylsulfonyl)benzyl)-1H-pyrrolo[3,2-c]pyridine-2-carboxamide

1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid (16.80 mg, 0.104 mmol),1H-benzo[d][1,2,3]triazol-1-ol (17.33 mg, 0.128 mmol) and EDC (25.3 mg,0.132 mmol) were dissolved in anhydrous THF (3 mL), followed by additionof Hunig's base (0.7 mL, 0.7 mmol). The mixture formed a slurrysolution. DMF (0.5 mL) was added. After stirring for 15 min at 65° C.,(4-(cyclohexylsulfonyl)phenyl)methanamine (25 mg, 0.099 mmol) in THF/DMF(1.0/0.3 mL) was added. The reaction mixture was stirred at 65° C.overnight, then diluted with ethyl acetate. The organic layer was washedsequentially with 5% aqueous acetic acid (×2), saturated aqueous sodiumbicarbonate (×2), and brine (×1). The organic layer was dried overanhydrous sodium sulfate, filtered and concentrated in vacuo to yield acrude product (40 mg). The crude was dissolved in DMSO and purified byreverse phase preparative HPLC to give the title compound (12.4 mg, 32%yield).

¹H NMR (300 MHz, DMSO-d₆): δ 12.05 (brs, 1H), 9.30 (t, 1H), 8.88 (s,1H), 8.16 (d, 1H), 7.76 (d, 2H), 7.54(d, 2H), 7.32 (d, 1H), 7.27 (s,1H), 4.57 (d, 2H), 3.08 (m, 1H), 1.78-1.66 (m, 4H), 1.51 (d, 1H),1.20-0.96 (m, 5H).

LC-MS: 398.0 (M+H).

It is understood that the person skilled in the art will be able toprepare the compounds of the present invention using methods known inthe art along with the general method of synthesis described herein.

Assays: Assay Example 1 Biochemical Inhibition Assay NAMPT ProteinPurification

Recombinant His-tagged NAMPT was produced in E. coli cells, purifiedover a Ni column, and further purified over a size-exclusion column byXTAL Biostructures.

The NAMPT Enzymatic Reaction

The NAMPT enzymatic reactions were carried out in Buffer A (50 mM HepespH 7.5, 50 mM NaCl, 5 mM MgCl₂, and 1 mM THP) in 96-well V-bottomplates. The compound titrations were performed in a separate dilutionplate by serially diluting the compounds in DMSO to make a 100× stock.Buffer A (89 μL) containing 33 nM of NAMPT protein was added to 1μL of100× compound plate containing controls (e.g. DMSO or blank). Thecompound and enzyme mix was incubated for 15 minutes at roomtemperature, then 10 μL of 100× X substrate and co-factors in Buffer Awere added to the test well to make a final concentration of 1 M NAM,100 μM 5-Phospho-D-ribose 1-diphosphate (PRPP), and 2.5 mM Adenosine5′-triphosphate (ATP). The reaction was allowed to proceed for 30minutes at room temperature, then was quenched with the addition of 11μL of a solution of formic acid and L-Cystathionine to make a finalconcentration of 1% formic acid and 10 μM L-Cystathionine. Backgroundand signal strength was determined by addition (or non-addition) of aserial dilution of NMN to a pre-quenched enzyme and cofactor mix.

Quantification of NMN

A mass spectrometry-based assay was used to measure the NAMPT reactionproduct (NMN) and the internal control (L-Cystathionine). NMN andL-Cystathionine were detected using the services of Biocius Lifescienceswith the RapidFire system. In short, the NMN and L-Cystathionine arebound to a graphitic carbon cartridge in 0.1% formic acid, eluted in 30%acetonitrile buffer, and injected into a Sciex 4000 mass spectrometer.The components of the sample were ionized with electrospray ionizationand the positive ions were detected. The Q1 (parent ion) and Q3(fragment ion) masses of NMN were 334.2 and 123.2, respectively. The Q1and Q3 for L-Cystathionine were 223.1 and 134.1, respectively. Thefragments are quantified and the analyzed by the following method.

% Inhibitions are Determined Using this Method.

First the NMN signal is normalized to the L-Cystathionine signal bydividing the NMN signal by the L-Cystathionine signal for each well. Thesignal from the background wells are averaged and subtracted from thetest plates. The compound treated cells re then assayed for % inhibitionby using this formula.

%Inh=100−100*x/y

wherein x denotes the average signal of the compound treated wells and ydenotes the average signal of the DMSO treated wells.

IC50s are Determined Using Excel and this Formula.

IC50=10̂(LOG 10(X)+(((50-% Inh at Cmpd Concentration1)/(XX-YY)*(LOG10(X)-LOG 10(Y))))

wherein X denotes the compound concentration 1, Y denotes the compoundconcentration 2, XX denotes the % inhibition at compound concentration 1(X), and YY denotes the % inhibition at compound concentration 2 (Y).

The NAMPT-inhibitor compounds of this invention have IC50 values thatare preferably under 1 μM, more preferably under 0.1 μM, and mostpreferably under 0.01 μM. Results for the compounds are provided inTable 3.

Assay Example 2 In-Vitro Cell Proliferation Assay

A2780 cells were seeded in 96-well plates at 1×10³ cells/well in 180 μLof culture medium (10% FBS, 1% Pen/Strep Amphotecricin B, RPMI-1640)with and without the addition of either β-nicotinamide mononucleotide(NMN) or nicotinamide (NAM). After overnight incubation at 37° C. and 5%CO₂, the compound titrations were performed in a separate dilution plateby serially diluting the compounds in DMSO to make a 1000× stock. Thecompounds were then further diluted to 10× final concentration inculture media, whereupon 20 μL of each dilution was added to the platedcells with controls (e.g. DMSO and blank) to make a final volume of 200μL. The final DMSO concentration in each well was 0.1%. The plates werethen incubated for 72 hours at 37° C. in a 5% CO₂ incubator. The numberof viable cells was then assessed using sulforhodamine B (SRB) assay.Cells were fixed at 4° C. for 1 hour with the addition of 50 p.1_, 30%trichloroacetic acid (TCA) to make a final concentration of 6 TCA. Theplates were washed four times with H₂O and allowed to dry for at least 1hour, whereupon 100 μL of a 4% SRB in 1% acetic acid solution was addedto each well and incubated at room temperature for at least 30 minutes.The plates were then washed three times with 1% acetic acid, dried, andtreated with 100 μL of 10 mM Tris-Base solution. The plates were thenread in a microplate reader at an absorbance of 570 nm. Background wasgenerated on a separate plate with media only.

Method for Determining % Inhibition

First, the signals from the background plate are averaged, then thebackground was subtracted from the test plates. The compound-treatedcells were then assayed for % inhibition by using the following formula:

% Inh=100−100*x/y

wherein x denotes the average signal of the compound-treated cells and ydenotes the average signal of the DMSO-treated cells.

Formula for Determining IC₅₀ Values:

IC50 =10̂(LOG 10(X)+(((50-% Inh at Cmpd Concentration 1)/(XX-YY)*(LOG10(X)-LOG 10(Y))))

wherein X denotes the compound concentration 1, Y denotes the compoundconcentration 2, XX denotes the % inhibition at compound concentration 1(X), and YY denotes the % inhibition at compound concentration 2 (Y).

Specificity of Cytotoxicity.

Inhibition of NAMPT could be reversed by the addition of NAM or NMN. Thespecificity of the compounds were determined via cell viability assay inthe presence of the compound and either NAM or NMN. Percent inhibitionswere determined using the method given above.

The NAMPT-inhibitor compounds of this invention have IC50 values thatare preferably under more preferably under 0.1 μM, and most preferablyunder 0.01 μM. Most preferable compounds of this invention are compoundsthat have both the enzymatic IC50-value and the A2780 IC 50-value under1 μM, more preferably both of the values are under 0.1 μM , and mostpreferably both of the values are under 0.01 μM. Results for thecompounds are provided in Table 3.

TABLE 3 A2780 Biochem IC50 IUPAC Name IC50 uM uM(E)-2-cyano-3-({4-[(5-fluoro-2- 0.0011 0.0030methoxyphenyl)sulfamoyl]phenyl}methyl)-1-(pyridin-4-yl)guanidine5-hydroxy-N-({4-[(4-phenylbenzene)sulfonyl]phenyl}methyl)-1H- 0.1-1  1-10 indole-2-carboxamide5-hydroxy-N-[(4-{[3-(morpholin-4-yl)benzene]sulfonyl}phenyl)methyl]-0.1-1   1-10 1H-indole-2-carboxamide5-hydroxy-N-[(4-{[3-(piperidin-1-yl)benzene]sulfonyl}phenyl)methyl]-0.1-1   1-10 1H-indole-2-carboxamide5-hydroxy-N-[(4-{[3-(pyrrolidin-1-yl)benzene]sulfonyl}phenyl)methyl]-0.1442 0.1-1 1H-indole-2-carboxamide5-hydroxy-N-{[4-(1-methyl-1H-indazole-4-sulfonyl)phenyl]methyl}-1H-0.1-1 >1.0 indole-2-carboxamide5-N-({4-[(3,5-difluorobenzene)sulfonyl]phenyl}methyl)pyridine-2,5-  1-10 0.661 diamido6-amino-N-({4-[(3,5-difluorobenzene)sulfonyl]phenyl}methyl)pyridine-0.0142 0.275 3-carboxamideN-({4-[(2,3,6-trimethoxybenzene)sulfonyl]phenyl}methyl)-1H- 0.07970.0663 pyrazolo[3,4-b]pyridine-5-carboxamideN-({4-[(2,3,6-trimethoxybenzene)sulfonyl]phenyl}methyl)furo[2,3- 0.03990.0667 c]pyridine-2-carboxamideN-({4-[(2,3-difluoro-6-methoxybenzene)sulfonyl]phenyl}methyl)-1H- 0.2040.0849 pyrrolo[3,2-c]pyridine-2-carboxamideN-({4-[(2,3-difluorobenzene)sulfonyl]phenyl}methyl)-1H-pyrazolo[3,4-0.0820 0.2786 b]pyridine-5-carboxamideN-({4-[(2,3-dimethoxy-5-methylbenzene)sulfonyl]phenyl}methyl)-1H- 0.14620.0586 pyrazolo[3,4-b]pyridine-5-carboxamide N-({4-[(2,3-dimethoxy-5-0.0152 0.007 methylbenzene)sulfonyl]phenyl}methyl)furo[2,3-c]pyridine-2-carboxamide N-({4-[(2,3-dimethoxy-5- 0.0042 0.0156methylbenzene)sulfonyl]phenyl}methyl)imidazo[1,2-a]pyrimidine-6-carboxamide N-({4-[(2,3-dimethoxybenzene)sulfonyl]phenyl}methyl)-1H-0.123 0.0833 pyrazolo[3,4-b]pyridine-5-carboxamideN-({4-[(2,3-dimethoxybenzene)sulfonyl]phenyl}methyl)-1H-pyrrolo[3,2-0.0117 0.0049 c]pyridine-2-carboxamideN-({4-[(2,3-dimethoxybenzene)sulfonyl]phenyl}methyl)furo[2,3- 0.00930.0136 c]pyridine-2-carboxamideN-({4-[(2,3-dimethoxybenzene)sulfonyl]phenyl}methyl)imidazo[1,2- 0.06870.0249 a]pyridine-6-carboxamideN-({4-[(2,3-dimethoxybenzene)sulfonyl]phenyl}methyl)imidazo[1,2- 0.01760.0776 a]pyrimidine-6-carboxamideN-({4-[(2,3-dimethylbenzene)sulfonyl]phenyl}methyl)furo[2,3- 0.05160.008 c]pyridine-2-carboxamideN-({4-[(2,3-dimethylbenzene)sulfonyl]phenyl}methyl)imidazo[1,2- 0.04330.00985 a]pyridine-6-carboxamideN-({4-[(2,3-dimethylbenzene)sulfonyl]phenyl}methyl)imidazo[1,2- 0.00410.0469 a]pyrimidine-6-carboxamideN-({4-[(2,4,5-trimethylbenzene)sulfonyl]phenyl}methyl)-1H- 0.0313 0.0193pyrazolo[3,4-b]pyridine-5-carboxamideN-({4-[(2,4,5-trimethylbenzene)sulfonyl]phenyl}methyl)furo[2,3- 0.00910.0141 c]pyridine-2-carboxamideN-({4-[(2,4,5-trimethylbenzene)sulfonyl]phenyl}methyl)imidazo[1,2-0.00934 0.0141 a]pyridine-6-carboxamideN-({4-[(2,4,5-trimethylbenzene)sulfonyl]phenyl}methyl)imidazo[1,2-0.0069 0.0240 a]pyrimidine-6-carboxamideN-({4-[(2,4,6-trimethylbenzene)sulfonyl]phenyl}methyl)-1H- 0.136 0.1-1pyrazolo[3,4-b]pyridine-5-carboxamideN-({4-[(2,4,6-trimethylbenzene)sulfonyl]phenyl}methyl)furo[2,3- 0.05920.1-1 c]pyridine-2-carboxamideN-({4-[(2,4,6-trimethylbenzene)sulfonyl]phenyl}methyl)imidazo[1,2-0.0288 0.1-1 a]pyrimidine-6-carboxamideN-({4-[(2,4-dichloro-3-methoxybenzene)sulfonyl]phenyl}methyl)-1H- 0.020.0147 pyrazolo[3,4-b]pyridine-5-carboxamide N-({4-[(2,4-dichloro-3-0.0177 0.0162methoxybenzene)sulfonyl]phenyl}methyl)furo[2,3-c]pyridine-2- carboxamideN-({4-[(2,4-dichloro-3- 0.0311 0.013methoxybenzene)sulfonyl]phenyl}methyl)imidazo[1,2-a]pyridine-6-carboxamide N-({4-[(2,4-dichloro-3- 0.0066 0.0255methoxybenzene)sulfonyl]phenyl}methyl)imidazo[1,2-a]pyrimidine-6-carboxamide N-({4-[(2,4-dichloro-3- 0.0051 0.0067methoxybenzene)sulfonyl]phenyl}methyl)thieno[2,3-c]pyridine-2-carboxamideN-({4-[(2,4-difluorobenzene)sulfonyl]phenyl}methyl)imidazo[1,2- 0.02830.0281 a]pyridine-6-carboxamideN-({4-[(2,4-dimethoxybenzene)sulfonyl]phenyl}methyl)-1H- 0.1744 0.0447pyrazolo[3,4-b]pyridine-5-carboxamideN-({4-[(2,4-dimethoxybenzene)sulfonyl]phenyl}methyl)imidazo[1,2- 0.05820.0151 a]pyridine-6-carboxamideN-({4-[(2,4-dimethoxybenzene)sulfonyl]phenyl}methyl)thieno[2,3- 0.00450.0016 c]pyridine-2-carboxamideN-({4-[(2,4-dimethylbenzene)sulfonyl]phenyl}methyl)-1H-pyrazolo[3,4-0.0612 0.0716 b]pyridine-5-carboxamideN-({4-[(2,4-dimethylbenzene)sulfonyl]phenyl}methyl)furo[2,3- 0.02180.024 c]pyridine-2-carboxamideN-({4-[(2,4-dimethylbenzene)sulfonyl]phenyl}methyl)imidazo[1,2- 0.02160.0321 a]pyridine-6-carboxamideN-({4-[(2,4-dimethylbenzene)sulfonyl]phenyl}methyl)imidazo[1,2- 0.00210.0492 a]pyrimidine-6-carboxamideN-({4-[(2,5-difluorobenzene)sulfonyl]phenyl}methyl)-1H- 0.1-1 0.3921pyrazolo[3,4-b]pyridine-5-carboxamideN-({4-[(2,5-dimethoxybenzene)sulfonyl]phenyl}methyl)-1H- 0.0398 0.0248pyrazolo[3,4-b]pyridine-5-carboxamideN-({4-[(2,5-dimethoxybenzene)sulfonyl]phenyl}methyl)furo[2,3- 0.01140.0063 c]pyridine-2-carboxamideN-({4-[(2,5-dimethoxybenzene)sulfonyl]phenyl}methyl)imidazo[1,2- 0.02020.0128 a]pyridine-6-carboxamideN-({4-[(2,5-dimethoxybenzene)sulfonyl]phenyl}methyl)imidazo[1,2- 0.00690.0457 a]pyrimidine-6-carboxamideN-({4-[(2,5-dimethylbenzene)sulfonyl]phenyl}methyl)-1H-pyrazolo[3,4-0.0209 0.0172 b]pyridine-5-carboxamideN-({4-[(2,5-dimethylbenzene)sulfonyl]phenyl}methyl)furo[2,3- 0.01810.0239 c]pyridine-2-carboxamideN-({4-[(2,5-dimethylbenzene)sulfonyl]phenyl}methyl)imidazo[1,2- 0.02930.0154 a]pyridine-6-carboxamideN-({4-[(2,6-dichloro-3-methylbenzene)sulfonyl]phenyl}methyl)furo[2,3-0.0108 0.0162 c]pyridine-2-carboxamide N-({4-[(2,6-dichloro-3- 0.00730.0560 methylbenzene)sulfonyl]phenyl}methyl)imidazo[1,2-a]pyrimidine-6-carboxamide N-({4-[(2,6-dichloro-3- 0.0044 0.0082methylbenzene)sulfonyl]phenyl}methyl)thieno[2,3-c]pyridine-2-carboxamideN-({4-[(2,6-dichlorobenzene)sulfonyl]phenyl}methyl)-1H-pyrazolo[3,4-0.1795   1-10 b]pyridine-5-carboxamideN-({4-[(2,6-dichlorobenzene)sulfonyl]phenyl}methyl)-1H-pyrrolo[3,2-0.0447 0.0135 c]pyridine-2-carboxamideN-({4-[(2,6-dichlorobenzene)sulfonyl]phenyl}methyl)furo[2,3- 0.01240.0601 c]pyridine-2-carboxamideN-({4-[(2,6-dichlorobenzene)sulfonyl]phenyl}methyl)imidazo[1,2- 0.00120.0188 a]pyridine-6-carboxamideN-({4-[(2,6-dichlorobenzene)sulfonyl]phenyl}methyl)imidazo[1,2- 0.01340.1-1 a]pyrimidine-6-carboxamideN-({4-[(2,6-dichlorobenzene)sulfonyl]phenyl}methyl)thieno[2,3- 0.00760.0182 c]pyridine-2-carboxamideN-({4-[(2,6-dimethoxy-4-methylbenzene)sulfonyl]phenyl}methyl)-1H- 0.1-10.1-1 pyrazolo[3,4-b]pyridine-5-carboxamide N-({4-[(2,6-dimethoxy-4-0.0050 0.0230methylbenzene)sulfonyl]phenyl}methyl)furo[2,3-c]pyridine-2- carboxamideN-({4-[(2,6-dimethylbenzene)sulfonyl]phenyl}methyl)-1H-pyrazolo[3,4-0.159 0.1-1 b]pyridine-5-carboxamideN-({4-[(2,6-dimethylbenzene)sulfonyl]phenyl}methyl)furo[2,3- 0.03230.1-1 c]pyridine-2-carboxamideN-({4-[(2-acetylbenzene)sulfonyl]phenyl}methyl)-1H-pyrazolo[3,4- 0.00360.0114 b]pyridine-5-carboxamideN-({4-[(2-acetylbenzene)sulfonyl]phenyl}methyl)furo[2,3-c]pyridine-2-0.0057 0.0065 carboxamideN-({4-[(2-acetylbenzene)sulfonyl]phenyl}methyl)imidazo[1,2- 0.00250.0082 a]pyrimidine-6-carboxamideN-({4-[(2-butoxy-4-fluorobenzene)sulfonyl]phenyl}methyl)-1H- 0.176 0.1-1pyrazolo[3,4-b]pyridine-5-carboxamideN-({4-[(2-butoxy-4-fluorobenzene)sulfonyl]phenyl}methyl)-1H- 0.03110.0055 pyrrolo[3,2-c]pyridine-2-carboxamideN-({4-[(2-butoxy-4-fluorobenzene)sulfonyl]phenyl}methyl)furo[2,3- 0.03350.0665 c]pyridine-2-carboxamideN-({4-[(2-butoxy-4-fluorobenzene)sulfonyl]phenyl}methyl)imidazo[1,2-0.0512 0.0062 a]pyridine-6-carboxamideN-({4-[(2-butoxy-4-fluorobenzene)sulfonyl]phenyl}methyl)imidazo[1,2-0.0073 0.0738 a]pyrimidine-6-carboxamideN-({4-[(2-butoxy-4-fluorobenzene)sulfonyl]phenyl}methyl)thieno[2,3-0.0070 0.0063 c]pyridine-2-carboxamideN-({4-[(2-butoxy-5-chlorobenzene)sulfonyl]phenyl}methyl)-1H- 0.1170.0737 pyrazolo[3,4-b]pyridine-5-carboxamideN-({4-[(2-butoxy-5-chlorobenzene)sulfonyl]phenyl}methyl)-1H- 0.01560.0083 pyrrolo[3,2-c]pyridine-2-carboxamideN-({4-[(2-butoxy-5-chlorobenzene)sulfonyl]phenyl}methyl)furo[2,3- 0.02430.0663 c]pyridine-2-carboxamideN-({4-[(2-butoxy-5-chlorobenzene)sulfonyl]phenyl}methyl)imidazo[1,2-0.0110 0.0080 a]pyridine-6-carboxamideN-({4-[(2-butoxy-5-chlorobenzene)sulfonyl]phenyl}methyl)imidazo[1,2-0.0037 0.0628 a]pyrimidine-6-carboxamideN-({4-[(2-butoxy-5-chlorobenzene)sulfonyl]phenyl}methyl)thieno[2,3-0.0073 0.0100 c]pyridine-2-carboxamideN-({4-[(2-butoxy-6-fluorobenzene)sulfonyl]phenyl}methyl)-1H- 0.00880.0056 pyrrolo[3,2-c]pyridine-2-carboxamideN-({4-[(2-butoxy-6-fluorobenzene)sulfonyl]phenyl}methyl)furo[2,3- 0.02560.0698 c]pyridine-2-carboxamideN-({4-[(2-butoxy-6-fluorobenzene)sulfonyl]phenyl}methyl)imidazo[1,2-0.0053 0.0069 a]pyridine-6-carboxamideN-({4-[(2-chloro-3-fluorobenzene)sulfonyl]phenyl}methyl)-1H- 0.07360.1-1 pyrazolo[3,4-b]pyridine-5-carboxamideN-({4-[(2-chloro-3-fluorobenzene)sulfonyl]phenyl}methyl)furo[2,3- 0.01700.0611 c]pyridine-2-carboxamideN-({4-[(2-chloro-4-fluorobenzene)sulfonyl]phenyl}methyl)furo[2,3- 0.01780.0634 c]pyridine-2-carboxamideN-({4-[(2-chloro-4-fluorobenzene)sulfonyl]phenyl}methyl)imidazo[1,2-0.0144 0.1-1 a]pyrimidine-6-carboxamideN-({4-[(2-chloro-4-methoxybenzene)sulfonyl]phenyl}methyl)-1H- 0.05160.0877 pyrazolo[3,4-b]pyridine-5-carboxamideN-({4-[(2-chloro-4-methoxybenzene)sulfonyl]phenyl}methyl)-1H- 0.00930.0145 pyrrolo[3,2-c]pyridine-2-carboxamide N-({4-[(2-chloro-4- 0.01670.0114 methoxybenzene)sulfonyl]phenyl}methyl)imidazo[1,2-a]pyridine-6-carboxamide N-({4-[(2-chloro-4- 0.0065 0.0669methoxybenzene)sulfonyl]phenyl}methyl)imidazo[1,2-a]pyrimidine-6-carboxamide N-({4-[(2-chloro-4- 0.0027 0.0055methoxybenzene)sulfonyl]phenyl}methyl)thieno[2,3-c]pyridine-2-carboxamide N-({4-[(2-chloro-4-methylbenzene)sulfonyl]phenyl}methyl)-1H-0.005 0.00278 pyrazolo[3,4-b]pyridine-5-carboxamideN-({4-[(2-chloro-4-methylbenzene)sulfonyl]phenyl}methyl)-1H- 0.00800.0027 pyrrolo[3,2-c]pyridine-2-carboxamideN-({4-[(2-chloro-4-methylbenzene)sulfonyl]phenyl}methyl)furo[2,3- 0.01410.0142 c]pyridine-2-carboxamideN-({4-[(2-chloro-4-methylbenzene)sulfonyl]phenyl}methyl)imidazo[1,2-0.0011 0.0009 a]pyridine-6-carboxamideN-({4-[(2-chloro-4-methylbenzene)sulfonyl]phenyl}methyl)imidazo[1,2-0.0015 0.0007 a]pyrimidine-6-carboxamideN-({4-[(2-chloro-4-methylbenzene)sulfonyl]phenyl}methyl)thieno[2,3-0.0249 0.0016 c]pyridine-2-carboxamideN-({4-[(2-chloro-5-fluorobenzene)sulfonyl]phenyl}methyl)-1H- 0.02810.0121 pyrrolo[3,2-c]pyridine-2-carboxamideN-({4-[(2-chloro-5-fluorobenzene)sulfonyl]phenyl}methyl)furo[2,3- 0.01630.0248 c]pyridine-2-carboxamideN-({4-[(2-chloro-5-fluorobenzene)sulfonyl]phenyl}methyl)imidazo[1,2-0.0210 0.0063 a]pyridine-6-carboxamideN-({4-[(2-chloro-5-fluorobenzene)sulfonyl]phenyl}methyl)imidazo[1,2-0.0105 0.0530 a]pyrimidine-6-carboxamideN-({4-[(2-chloro-5-fluorobenzene)sulfonyl]phenyl}methyl)thieno[2,3-0.0042 0.0057 c]pyridine-2-carboxamideN-({4-[(2-chloro-5-methoxybenzene)sulfonyl]phenyl}methyl)-1H- 0.02470.0668 pyrazolo[3,4-b]pyridine-5-carboxamideN-({4-[(2-chloro-5-methoxybenzene)sulfonyl]phenyl}methyl)-1H- 0.01100.0097 pyrrolo[3,2-c]pyridine-2-carboxamideN-({4-[(2-chloro-5-methoxybenzene)sulfonyl]phenyl}methyl)furo[2,3-0.0026 0.0206 c]pyridine-2-carboxamide N-({4-[(2-chloro-5- 0.0056 0.0027methoxybenzene)sulfonyl]phenyl}methyl)imidazo[1,2-a]pyridine-6-carboxamide N-({4-[(2-chloro-5- 0.0061 0.0515methoxybenzene)sulfonyl]phenyl}methyl)imidazo[1,2-a]pyrimidine-6-carboxamide N-({4-[(2-chloro-5- 0.0049 0.0053methoxybenzene)sulfonyl]phenyl}methyl)thieno[2,3-c]pyridine-2-carboxamide N-({4-[(2-chloro-5-methylbenzene)sulfonyl]phenyl}methyl)-1H-0.0602 0.0659 pyrazolo[3,4-b]pyridine-5-carboxamideN-({4-[(2-chloro-5-methylbenzene)sulfonyl]phenyl}methyl)-1H- 0.01880.0091 pyrrolo[3,2-c]pyridine-2-carboxamideN-({4-[(2-chloro-5-methylbenzene)sulfonyl]phenyl}methyl)furo[2,3- 0.01780.0149 c]pyridine-2-carboxamideN-({4-[(2-chloro-5-methylbenzene)sulfonyl]phenyl}methyl)imidazo[1,2-0.0056 0.0046 a]pyridine-6-carboxamideN-({4-[(2-chloro-5-methylbenzene)sulfonyl]phenyl}methyl)imidazo[1,2-0.0057 0.0225 a]pyrimidine-6-carboxamideN-({4-[(2-chloro-5-methylbenzene)sulfonyl]phenyl}methyl)thieno[2,3-0.0022 0.0049 c]pyridine-2-carboxamideN-({4-[(2-chloro-6-fluorobenzene)sulfonyl]phenyl}methyl)-1H- 0.11420.0371 pyrrolo[3,2-c]pyridine-2-carboxamideN-({4-[(2-chloro-6-fluorobenzene)sulfonyl]phenyl}methyl)imidazo[1,2-0.1722 0.0766 a]pyridine-6-carboxamideN-({4-[(2-chloro-6-methoxybenzene)sulfonyl]phenyl}methyl)furo[2,3-0.0167 0.0214 c]pyridine-2-carboxamide N-({4-[(2-chloro-6- 0.0202 0.0258methoxybenzene)sulfonyl]phenyl}methyl)imidazo[1,2-a]pyridine-6-carboxamide N-({4-[(2-chloro-6- 0.0027 0.0029methoxybenzene)sulfonyl]phenyl}methyl)thieno[2,3-c]pyridine-2-carboxamideN-({4-[(2-chlorobenzene)sulfonyl]phenyl}methyl)-1H-pyrazolo[3,4- 0.0925  1-0.1 b]pyridine-5-carboxamideN-({4-[(2-chlorobenzene)sulfonyl]phenyl}methyl)imidazo[1,2- 0.02410.0567 a]pyridine-6-carboxamideN-({4-[(2-chlorobenzene)sulfonyl]phenyl}methyl)thieno[2,3-c]pyridine-0.0024 0.0066 2-carboxamideN-({4-[(2-cyanobenzene)sulfonyl]phenyl}methyl)-1H-pyrazolo[3,4- 0.1310.1-1 b]pyridine-5-carboxamideN-({4-[(2-cyanobenzene)sulfonyl]phenyl}methyl)-1H-pyrrolo[3,2- 0.02530.0629 c]pyridine-2-carboxamideN-({4-[(2-cyanobenzene)sulfonyl]phenyl}methyl)furo[2,3-c]pyridine-2-0.0246 0.0635 carboxamideN-({4-[(2-cyanobenzene)sulfonyl]phenyl}methyl)imidazo[1,2- 0.0156 0.0613a]pyridine-6-carboxamideN-({4-[(2-cyanobenzene)sulfonyl]phenyl}methyl)thieno[2,3-c]pyridine-0.0146 0.0676 2-carboxamideN-({4-[(2-ethoxy-4-fluorobenzene)sulfonyl]phenyl}methyl)-1H- 0.08630.0670 pyrazolo[3,4-b]pyridine-5-carboxamideN-({4-[(2-ethoxy-4-fluorobenzene)sulfonyl]phenyl}methyl)-1H- 0.00340.0018 pyrrolo[3,2-c]pyridine-2-carboxamideN-({4-[(2-ethoxy-4-fluorobenzene)sulfonyl]phenyl}methyl)furo[2,3- 0.00770.0069 c]pyridine-2-carboxamideN-({4-[(2-ethoxy-4-fluorobenzene)sulfonyl]phenyl}methyl)imidazo[1,2-0.0314 0.0015 a]pyridine-6-carboxamideN-({4-[(2-ethoxy-4-fluorobenzene)sulfonyl]phenyl}methyl)imidazo[1,2-0.0071 0.0143 a]pyrimidine-6-carboxamideN-({4-[(2-ethoxy-4-fluorobenzene)sulfonyl]phenyl}methyl)thieno[2,3-0.0038 0.0009 c]pyridine-2-carboxamideN-({4-[(2-ethoxy-6-fluorobenzene)sulfonyl]phenyl}methyl)furo[2,3- 0.01700.0283 c]pyridine-2-carboxamideN-({4-[(2-ethoxybenzene)sulfonyl]phenyl}methyl)-1H-pyrazolo[3,4- 0.04930.0269 b]pyridine-5-carboxamideN-({4-[(2-ethoxybenzene)sulfonyl]phenyl}methyl)furo[2,3-c]pyridine-2-0.0659 0.006 carboxamideN-({4-[(2-ethoxybenzene)sulfonyl]phenyl}methyl)imidazo[1,2- 0.02030.00339 a]pyridine-6-carboxamideN-({4-[(2-ethoxybenzene)sulfonyl]phenyl}methyl)imidazo[1,2- 0.00100.0071 a]pyrimidine-6-carboxamideN-({4-[(2-ethylbenzene)sulfonyl]phenyl}methyl)-1H-pyrazolo[3,4- 0.00840.013 b]pyridine-5-carboxamideN-({4-[(2-ethylbenzene)sulfonyl]phenyl}methyl)furo[2,3-c]pyridine-2-0.0054 0.0129 carboxamideN-({4-[(2-ethylbenzene)sulfonyl]phenyl}methyl)imidazo[1,2-a]pyridine-0.0302 0.0129 6-carboxamideN-({4-[(2-ethylbenzene)sulfonyl]phenyl}methyl)imidazo[1,2- 0.0025 0.0249a]pyrimidine-6-carboxamideN-({4-[(2-fluoro-3-methoxybenzene)sulfonyl]phenyl}methyl)-1H- 0.00860.0563 pyrazolo[3,4-b]pyridine-5-carboxamide N-({4-[(2-fluoro-3- 0.0330.0135 methoxybenzene)sulfonyl]phenyl}methyl)imidazo[1,2-a]pyridine-6-carboxamide N-({4-[(2-fluoro-3-methylbenzene)sulfonyl]phenyl}methyl)-1H-0.0197 0.0239 pyrazolo[3,4-b]pyridine-5-carboxamideN-({4-[(2-fluoro-3-methylbenzene)sulfonyl]phenyl}methyl)-1H- 0.07580.0070 pyrrolo[3,2-c]pyridine-2-carboxamideN-({4-[(2-fluoro-3-methylbenzene)sulfonyl]phenyl}methyl)furo[2,3- 0.00630.0079 c]pyridine-2-carboxamideN-({4-[(2-fluoro-3-methylbenzene)sulfonyl]phenyl}methyl)imidazo[1,2-0.0075 0.0033 a]pyridine-6-carboxamideN-({4-[(2-fluoro-3-methylbenzene)sulfonyl]phenyl}methyl)imidazo[1,2-0.0032 0.0215 a]pyrimidine-6-carboxamideN-({4-[(2-fluoro-3-methylbenzene)sulfonyl]phenyl}methyl)thieno[2,3-0.0107 0.0033 c]pyridine-2-carboxamideN-({4-[(2-fluoro-4-methoxybenzene)sulfonyl]phenyl}methyl)-1H- 0.12030.2067 pyrazolo[3,4-b]pyridine-5-carboxamide N-({4-[(2-fluoro-4- 0.04130.0229 methoxybenzene)sulfonyl]phenyl}methyl)imidazo[1,2-a]pyridine-6-carboxamideN-({4-[(2-fluoro-4-methylbenzene)sulfonyl]phenyl}methyl)furo[2,3- 0.01230.0253 c]pyridine-2-carboxamideN-({4-[(2-fluoro-4-methylbenzene)sulfonyl]phenyl}methyl)imidazo[1,2-0.0214 0.0247 a]pyridine-6-carboxamideN-({4-[(2-fluoro-4-methylbenzene)sulfonyl]phenyl}methyl)imidazo[1,2-0.0063 0.0614 a]pyrimidine-6-carboxamideN-({4-[(2-fluoro-5-methoxybenzene)sulfonyl]phenyl}methyl)-1H- 0.1390.1-1 pyrazolo[3,4-b]pyridine-5-carboxamideN-({4-[(2-fluoro-5-methoxybenzene)sulfonyl]phenyl}methyl)-1H- 0.07780.0144 pyrrolo[3,2-c]pyridine-2-carboxamideN-({4-[(2-fluoro-5-methoxybenzene)sulfonyl]phenyl}methyl)furo[2,3-0.0268 0.0637 c]pyridine-2-carboxamide N-({4-[(2-fluoro-5- 0.0047 0.0128methoxybenzene)sulfonyl]phenyl}methyl)imidazo[1,2-a]pyridine-6-carboxamide N-({4-[(2-fluoro-5- 0.0104 0.0629methoxybenzene)sulfonyl]phenyl}methyl)imidazo[1,2-a]pyrimidine-6-carboxamideN-({4-[(2-fluoro-5-methoxybenzene)sulfonyl]phenyl}methyl)thieno[2,3-0.0023 0.0128 c]pyridine-2-carboxamideN-({4-[(2-fluoro-5-methylbenzene)sulfonyl]phenyl}methyl)-1H- 0.02410.0716 pyrazolo[3,4-b]pyridine-5-carboxamideN-({4-[(2-fluoro-5-methylbenzene)sulfonyl]phenyl}methyl)furo[2,3- 0.00590.0134 c]pyridine-2-carboxamideN-({4-[(2-fluoro-5-methylbenzene)sulfonyl]phenyl}methyl)imidazo[1,2-0.0068 0.0275 a]pyrimidine-6-carboxamide N-({4-[(2-fluoro-6- 0.04810.0264 methoxybenzene)sulfonyl]phenyl}methyl)imidazo[1,2-a]pyridine-6-carboxamideN-({4-[(2-fluoro-6-propoxybenzene)sulfonyl]phenyl}methyl)furo[2,3-0.0133 0.0142 c]pyridine-2-carboxamide N-({4-[(2-fluoro-6- 0.0914 0.0010propoxybenzene)sulfonyl]phenyl}methyl)imidazo[1,2-a]pyridine-6-carboxamideN-({4-[(2-fluoro-6-propoxybenzene)sulfonyl]phenyl}methyl)thieno[2,3-0.0115 0.0293 c]pyridine-2-carboxamideN-({4-[(2-fluorobenzene)sulfonyl]phenyl}methyl)furo[2,3-c]pyridine-2-0.0418 0.1-1 carboxamideN-({4-[(2-methanesulfonylbenzene)sulfonyl]phenyl}methyl)-1H- 0.20220.1-1 pyrazolo[3,4-b]pyridine-5-carboxamideN-({4-[(2-methanesulfonylbenzene)sulfonyl]phenyl}methyl)furo[2,3- 0.05420.1-1 c]pyridine-2-carboxamideN-({4-[(2-methoxy-5-methylbenzene)sulfonyl]phenyl}methyl)-1H- 0.05630.0244 pyrazolo[3,4-b]pyridine-5-carboxamideN-({4-[(2-methoxy-5-methylbenzene)sulfonyl]phenyl}methyl)furo[2,3-0.0133 0.0068 c]pyridine-2-carboxamide N-({4-[(2-methoxy-5- 0.04310.0117 methylbenzene)sulfonyl]phenyl}methyl)imidazo[1,2-a]pyridine-6-carboxamide N-({4-[(2-methoxy-5- 0.0039 0.0072methylbenzene)sulfonyl]phenyl}methyl)imidazo[1,2-a]pyrimidine-6-carboxamideN-({4-[(2-methoxybenzene)sulfonyl]phenyl}methyl)-1H-pyrazolo[3,4- 0.06830.0618 b]pyridine-5-carboxamideN-({4-[(2-methoxybenzene)sulfonyl]phenyl}methyl)furo[2,3-c]pyridine-0.0189 0.0265 2-carboxamideN-({4-[(2-methoxybenzene)sulfonyl]phenyl}methyl)imidazo[1,2- 0.02650.0153 a]pyridine-6-carboxamideN-({4-[(2-methoxybenzene)sulfonyl]phenyl}methyl)imidazo[1,2- 0.00390.0747 a]pyrimidine-6-carboxamideN-({4-[(2-methyl-4-propoxybenzene)sulfonyl]phenyl}methyl)-1H- 0.06440.0794 pyrazolo[3,4-b]pyridine-5-carboxamideN-({4-[(2-methyl-4-propoxybenzene)sulfonyl]phenyl}methyl)-1H- 0.03050.0221 pyrrolo[3,2-c]pyridine-2-carboxamideN-({4-[(2-methyl-4-propoxybenzene)sulfonyl]phenyl}methyl)furo[2,3-0.0225 0.0596 c]pyridine-2-carboxamide N-({4-[(2-methyl-4- 0.0092 0.0133propoxybenzene)sulfonyl]phenyl}methyl)imidazo[1,2-a]pyridine-6-carboxamide N-({4-[(2-methyl-4- 0.0100 0.0518propoxybenzene)sulfonyl]phenyl}methyl)imidazo[1,2-a]pyrimidine-6-carboxamide N-({4-[(2-methyl-4- 0.0129 0.0017propoxybenzene)sulfonyl]phenyl}methyl)thieno[2,3-c]pyridine-2-carboxamideN-({4-[(2-methylbenzene)sulfonyl]phenyl}methyl)-1H-pyrazolo[3,4- 0.0926  1-0.1 b]pyridine-5-carboxamideN-({4-[(2-methylbenzene)sulfonyl]phenyl}methyl)furo[2,3-c]pyridine-2-0.0152 0.0433 carboxamideN-({4-[(2-methylbenzene)sulfonyl]phenyl}methyl)imidazo[1,2- 0.06690.0912 a]pyridine-6-carboxamideN-({4-[(2-phenoxybenzene)sulfonyl]phenyl}methyl)-1H-pyrazolo[3,4- 0.1-10.1-1 b]pyridine-5-carboxamideN-({4-[(2-phenoxybenzene)sulfonyl]phenyl}methyl)furo[2,3-c]pyridine-0.0204   1-10 2-carboxamideN-({4-[(2-phenoxybenzene)sulfonyl]phenyl}methyl)imidazo[1,2- 0.06360.0607 a]pyridine-6-carboxamideN-({4-[(2-phenoxybenzene)sulfonyl]phenyl}methyl)imidazo[1,2- 0.00850.1-1 a]pyrimidine-6-carboxamideN-({4-[(3,4-dichlorobenzene)sulfonyl]phenyl}methyl)-1H-pyrazolo[3,4-0.0067 0.0055 b]pyridine-5-carboxamideN-({4-[(3,4-dichlorobenzene)sulfonyl]phenyl}methyl)furo[2,3- 0.01040.0048 c]pyridine-2-carboxamideN-({4-[(3,4-dichlorobenzene)sulfonyl]phenyl}methyl)imidazo[1,2- 0.00150.0017 a]pyrimidine-6-carboxamideN-({4-[(3,4-difluorobenzene)sulfonyl]phenyl}methyl)-1H-pyrazolo[3,4-0.0542 0.0289 b]pyridine-5-carboxamideN-({4-[(3,4-difluorobenzene)sulfonyl]phenyl}methyl)furo[2,3- 0.01680.013 c]pyridine-2-carboxamideN-({4-[(3,4-difluorobenzene)sulfonyl]phenyl}methyl)imidazo[1,2- 0.00410.0363 a]pyrimidine-6-carboxamideN-({4-[(3,4-dimethoxybenzene)sulfonyl]phenyl}methyl)-1H- 0.0206 0.0056pyrazolo[3,4-b]pyridine-5-carboxamideN-({4-[(3,4-dimethoxybenzene)sulfonyl]phenyl}methyl)furo[2,3- 0.00620.0038 c]pyridine-2-carboxamideN-({4-[(3,4-dimethoxybenzene)sulfonyl]phenyl}methyl)imidazo[1,2- 0.0120.00251 a]pyridine-6-carboxamideN-({4-[(3,4-dimethoxybenzene)sulfonyl]phenyl}methyl)imidazo[1,2- 0.00290.0073 a]pyrimidine-6-carboxamideN-({4-[(3,4-dimethylbenzene)sulfonyl]phenyl}methyl)-1H-pyrazolo[3,4-0.0051 0.0034 b]pyridine-5-carboxamideN-({4-[(3,4-dimethylbenzene)sulfonyl]phenyl}methyl)furo[2,3- 0.01500.003 c]pyridine-2-carboxamideN-({4-[(3,4-dimethylbenzene)sulfonyl]phenyl}methyl)imidazo[1,2- 0.01110.00297 a]pyridine-6-carboxamideN-({4-[(3,4-dimethylbenzene)sulfonyl]phenyl}methyl)imidazo[1,2- 0.00110.0016 a]pyrimidine-6-carboxamideN-({4-[(3,5-dichlorobenzene)sulfonyl]phenyl}methyl)-1H-pyrazolo[3,4-0.0067 0.0021 b]pyridine-5-carboxamideN-({4-[(3,5-dichlorobenzene)sulfonyl]phenyl}methyl)-1H-pyrrolo[3,2-0.001 0.0004 c]pyridine-2-carboxamideN-({4-[(3,5-dichlorobenzene)sulfonyl]phenyl}methyl)imidazo[1,2- 0.005490.00128 a]pyridine-6-carboxamideN-({4-[(3,5-difluorobenzene)sulfonyl]phenyl}methyl)-1H-pyrazolo[3,4-0.008 0.007 b]pyridine-5-carboxamideN-({4-[(3,5-difluorobenzene)sulfonyl]phenyl}methyl)imidazo[1,2- 0.0060.0015 a]pyridine-6-carboxamideN-({4-[(3,5-difluorobenzene)sulfonyl]phenyl}methyl)imidazo[1,2- 0.0020.003 a]pyrimidine-6-carboxamideN-({4-[(3,5-dimethoxybenzene)sulfonyl]phenyl}methyl)-1H- 0.0026 0.0022pyrazolo[3,4-b]pyridine-5-carboxamideN-({4-[(3,5-dimethoxybenzene)sulfonyl]phenyl}methyl)-1H-pyrrolo[3,2-0.0044 0.0015 c]pyridine-2-carboxamideN-({4-[(3,5-dimethoxybenzene)sulfonyl]phenyl}methyl)furo[2,3- 0.00270.0017 c]pyridine-2-carboxamideN-({4-[(3,5-dimethoxybenzene)sulfonyl]phenyl}methyl)imidazo[1,2- 0.00320.0015 a]pyridine-6-carboxamideN-({4-[(3,5-dimethoxybenzene)sulfonyl]phenyl}methyl)imidazo[1,2- 0.00240.0016 a]pyrimidine-6-carboxamideN-({4-[(3,5-dimethoxybenzene)sulfonyl]phenyl}methyl)thieno[2,3- 0.00130.0009 c]pyridine-2-carboxamideN-({4-[(3,5-dimethylbenzene)sulfonyl]phenyl}methyl)-1H-pyrazolo[3,4-0.0104 0.0061 b]pyridine-5-carboxamideN-({4-[(3,5-dimethylbenzene)sulfonyl]phenyl}methyl)furo[2,3- 0.01670.0028 c]pyridine-2-carboxamideN-({4-[(3,5-dimethylbenzene)sulfonyl]phenyl}methyl)imidazo[1,2- 0.006760.00317 a]pyridine-6-carboxamideN-({4-[(3,5-dimethylbenzene)sulfonyl]phenyl}methyl)imidazo[1,2- 0.00170.0020 a]pyrimidine-6-carboxamideN-({4-[(3-acetylbenzene)sulfonyl]phenyl}methyl)-1H-pyrazolo[3,4- 0.01000.0129 b]pyridine-5-carboxamideN-({4-[(3-acetylbenzene)sulfonyl]phenyl}methyl)furo[2,3-c]pyridine-2-0.0176 0.008 carboxamideN-({4-[(3-acetylbenzene)sulfonyl]phenyl}methyl)imidazo[1,2- 0.01250.00637 a]pyridine-6-carboxamideN-({4-[(3-acetylbenzene)sulfonyl]phenyl}methyl)imidazo[1,2- 0.00180.0105 a]pyrimidine-6-carboxamideN-({4-[(3-butoxybenzene)sulfonyl]phenyl}methyl)-1H-pyrazolo[3,4- 0.03840.0675 b]pyridine-5-carboxamideN-({4-[(3-butoxybenzene)sulfonyl]phenyl}methyl)-1H-pyrrolo[3,2- 0.01150.0216 c]pyridine-2-carboxamideN-({4-[(3-butoxybenzene)sulfonyl]phenyl}methyl)furo[2,3-c]pyridine-2-0.0123 0.0695 carboxamideN-({4-[(3-butoxybenzene)sulfonyl]phenyl}methyl)imidazo[1,2- 0.00470.0180 a]pyridine-6-carboxamideN-({4-[(3-butoxybenzene)sulfonyl]phenyl}methyl)thieno[2,3- 0.0033 0.0387c]pyridine-2-carboxamideN-({4-[(3-chloro-2-fluorobenzene)sulfonyl]phenyl}methyl)furo[2,3- 0.01090.0128 c]pyridine-2-carboxamideN-({4-[(3-chloro-2-fluorobenzene)sulfonyl]phenyl}methyl)imidazo[1,2-0.0024 0.0176 a]pyrimidine-6-carboxamideN-({4-[(3-chloro-2-methoxybenzene)sulfonyl]phenyl}methyl)furo[2,3-0.0192 0.0623 c]pyridine-2-carboxamideN-({4-[(3-chloro-2-methylbenzene)sulfonyl]phenyl}methyl)-1H- 0.03690.0161 pyrazolo[3,4-b]pyridine-5-carboxamideN-({4-[(3-chloro-2-methylbenzene)sulfonyl]phenyl}methyl)-1H- 0.06250.0120 pyrrolo[3,2-c]pyridine-2-carboxamideN-({4-[(3-chloro-2-methylbenzene)sulfonyl]phenyl}methyl)furo[2,3- 0.00260.0016 c]pyridine-2-carboxamideN-({4-[(3-chloro-2-methylbenzene)sulfonyl]phenyl}methyl)imidazo[1,2-0.0257 0.0050 a]pyridine-6-carboxamideN-({4-[(3-chloro-2-methylbenzene)sulfonyl]phenyl}methyl)imidazo[1,2-0.0043 0.0265 a]pyrimidine-6-carboxamideN-({4-[(3-chloro-2-methylbenzene)sulfonyl]phenyl}methyl)thieno[2,3-0.0572 0.0071 c]pyridine-2-carboxamideN-({4-[(3-chloro-4-methoxybenzene)sulfonyl]phenyl}methyl)-1H- 0.00400.0036 pyrazolo[3,4-b]pyridine-5-carboxamideN-({4-[(3-chloro-4-methoxybenzene)sulfonyl]phenyl}methyl)-1H- 0.01070.0021 pyrrolo[3,2-c]pyridine-2-carboxamideN-({4-[(3-chloro-4-methoxybenzene)sulfonyl]phenyl}methyl)furo[2,3-0.0073 0.0018 c]pyridine-2-carboxamide N-({4-[(3-chloro-4- 0.0018 0.0018methoxybenzene)sulfonyl]phenyl}methyl)imidazo[1,2-a]pyrimidine-6-carboxamide N-({4-[(3-chloro-4- 0.0050 0.0016methoxybenzene)sulfonyl]phenyl}methyl)thieno[2,3-c]pyridine-2-carboxamide N-({4-[(3-chloro-4-methylbenzene)sulfonyl]phenyl}methyl)-1H-0.0061 0.0019 pyrazolo[3,4-b]pyridine-5-carboxamideN-({4-[(3-chloro-4-methylbenzene)sulfonyl]phenyl}methyl)-1H- 0.00830.0025 pyrrolo[3,2-c]pyridine-2-carboxamideN-({4-[(3-chloro-4-methylbenzene)sulfonyl]phenyl}methyl)furo[2,3- 0.05280.0017 c]pyridine-2-carboxamideN-({4-[(3-chloro-4-methylbenzene)sulfonyl]phenyl}methyl)imidazo[1,2-0.0018 0.0012 a]pyrimidine-6-carboxamideN-({4-[(3-chloro-4-methylbenzene)sulfonyl]phenyl}methyl)thieno[2,3-0.0051 0.0010 c]pyridine-2-carboxamideN-({4-[(3-chloro-4-propoxybenzene)sulfonyl]phenyl}methyl)-1H- 0.00790.00958 pyrazolo[3,4-b]pyridine-5-carboxamideN-({4-[(3-chloro-4-propoxybenzene)sulfonyl]phenyl}methyl)-1H- 0.07400.0078 pyrrolo[3,2-c]pyridine-2-carboxamideN-({4-[(3-chloro-4-propoxybenzene)sulfonyl]phenyl}methyl)furo[2,3-0.0049 0.0119 c]pyridine-2-carboxamide N-({4-[(3-chloro-4- 0.0065 0.0060propoxybenzene)sulfonyl]phenyl}methyl)imidazo[1,2-a]pyridine-6-carboxamide N-({4-[(3-chloro-4- 0.0039 0.0024propoxybenzene)sulfonyl]phenyl}methyl)imidazo[1,2-a]pyrimidine-6-carboxamideN-({4-[(3-chloro-4-propoxybenzene)sulfonyl]phenyl}methyl)thieno[2,3-0.0151 0.0174 c]pyridine-2-carboxamideN-({4-[(3-chloro-5-fluorobenzene)sulfonyl]phenyl}methyl)-1H- 0.01330.0060 pyrazolo[3,4-b]pyridine-5-carboxamideN-({4-[(3-chloro-5-fluorobenzene)sulfonyl]phenyl}methyl)-1H- 0.00990.0014 pyrrolo[3,2-c]pyridine-2-carboxamideN-({4-[(3-chloro-5-fluorobenzene)sulfonyl]phenyl}methyl)furo[2,3- 0.01780.0031 c]pyridine-2-carboxamideN-({4-[(3-chloro-5-fluorobenzene)sulfonyl]phenyl}methyl)imidazo[1,2-0.0039 0.0003 a]pyridine-6-carboxamideN-({4-[(3-chloro-5-fluorobenzene)sulfonyl]phenyl}methyl)imidazo[1,2-0.0024 0.0029 a]pyrimidine-6-carboxamideN-({4-[(3-chloro-5-fluorobenzene)sulfonyl]phenyl}methyl)thieno[2,3-0.0014 0.0006 c]pyridine-2-carboxamideN-({4-[(3-chloro-5-methoxybenzene)sulfonyl]phenyl}methyl)-1H- 0.00930.0025 pyrazolo[3,4-b]pyridine-5-carboxamideN-({4-[(3-chloro-5-methoxybenzene)sulfonyl]phenyl}methyl)-1H- 0.01700.0025 pyrrolo[3,2-c]pyridine-2-carboxamideN-({4-[(3-chloro-5-methoxybenzene)sulfonyl]phenyl}methyl)furo[2,3-0.0265 0.0015 c]pyridine-2-carboxamide N-({4-[(3-chloro-5- 0.0092 0.0015methoxybenzene)sulfonyl]phenyl}methyl)imidazo[1,2-a]pyridine-6-carboxamide N-({4-[(3-chloro-5- 0.0013 0.0008methoxybenzene)sulfonyl]phenyl}methyl)imidazo[1,2-a]pyrimidine-6-carboxamide N-({4-[(3-chloro-5- 0.0041 0.0011methoxybenzene)sulfonyl]phenyl}methyl)thieno[2,3-c]pyridine-2-carboxamide N-({4-[(3-chloro-5-methylbenzene)sulfonyl]phenyl}methyl)-1H-0.0062 0.0026 pyrazolo[3,4-b]pyridine-5-carboxamideN-({4-[(3-chloro-5-methylbenzene)sulfonyl]phenyl}methyl)furo[2,3- 0.02690.0018 c]pyridine-2-carboxamideN-({4-[(3-chloro-5-methylbenzene)sulfonyl]phenyl}methyl)furo[2,3- 0.00130.0008 c]pyridine-2-carboxamideN-({4-[(3-chloro-5-methylbenzene)sulfonyl]phenyl}methyl)imidazo[1,2-0.0064 0.002 a]pyridine-6-carboxamideN-({4-[(3-chloro-5-methylbenzene)sulfonyl]phenyl}methyl)imidazo[1,2-0.0048 0.0023 a]pyrimidine-6-carboxamideN-({4-[(3-chloro-5-methylbenzene)sulfonyl]phenyl}methyl)thieno[2,3-0.0045 0.0016 c]pyridine-2-carboxamideN-({4-[(3-chlorobenzene)sulfonyl]phenyl}methyl)-1H-pyrazolo[3,4- 0.0070.006 b]pyridine-5-carboxamideN-({4-[(3-chlorobenzene)sulfonyl]phenyl}methyl)-1H-pyrrolo[3,2- 0.00390.013 b]pyridine-2-carboxamideN-({4-[(3-chlorobenzene)sulfonyl]phenyl}methyl)furo[2,3-c]pyridine-2-0.0060 0.0033 carboxamideN-({4-[(3-chlorobenzene)sulfonyl]phenyl}methyl)imidazo[1,2- 0.009080.00307 a]pyridine-6-carboxamideN-({4-[(3-chlorobenzene)sulfonyl]phenyl}methyl)imidazo[1,2- 0.00130.0012 a]pyrimidine-6-carboxamideN-({4-[(3-cyanobenzene)sulfonyl]phenyl}methyl)-1H-pyrazolo[3,4- 0.01850.00954 b]pyridine-5-carboxamideN-({4-[(3-cyanobenzene)sulfonyl]phenyl}methyl)-1H-pyrrolo[3,2- 0.01210.0113 c]pyridine-2-carboxamideN-({4-[(3-cyanobenzene)sulfonyl]phenyl}methyl)furo[2,3-c]pyridine-2-0.0154 0.0126 carboxamideN-({4-[(3-cyanobenzene)sulfonyl]phenyl}methyl)imidazo[1,2- 0.0059 0.0192a]pyrimidine-6-carboxamideN-({4-[(3-cyanobenzene)sulfonyl]phenyl}methyl)thieno[2,3-c]pyridine-0.0035 0.0056 2-carboxamideN-({4-[(3-ethoxy-2-fluorobenzene)sulfonyl]phenyl}methyl)-1H- 0.03120.0116 pyrrolo[3,2-c]pyridine-2-carboxamideN-({4-[(3-ethoxy-2-fluorobenzene)sulfonyl]phenyl}methyl)furo[2,3- 0.01750.0227 c]pyridine-2-carboxamideN-({4-[(3-ethoxy-2-fluorobenzene)sulfonyl]phenyl}methyl)imidazo[1,2-0.0050 0.0062 a]pyridine-6-carboxamideN-({4-[(3-ethoxy-2-fluorobenzene)sulfonyl]phenyl}methyl)imidazo[1,2-0.0040 0.0197 a]pyrimidine-6-carboxamideN-({4-[(3-ethoxy-2-fluorobenzene)sulfonyl]phenyl}methyl)thieno[2,3-0.0037 0.0129 c]pyridine-2-carboxamideN-({4-[(3-ethoxy-4-fluorobenzene)sulfonyl]phenyl}methyl)-1H- 0.02610.012 pyrazolo[3,4-b]pyridine-5-carboxamideN-({4-[(3-ethoxy-4-fluorobenzene)sulfonyl]phenyl}methyl)-1H- 0.08240.0044 pyrrolo[3,2-c]pyridine-2-carboxamideN-({4-[(3-ethoxy-4-fluorobenzene)sulfonyl]phenyl}methyl)furo[2,3- 0.01100.0072 c]pyridine-2-carboxamideN-({4-[(3-ethoxy-4-fluorobenzene)sulfonyl]phenyl}methyl)imidazo[1,2-0.0170 0.006 a]pyridine-6-carboxamideN-({4-[(3-ethoxy-4-fluorobenzene)sulfonyl]phenyl}methyl)imidazo[1,2-0.0003 0.0078 a]pyrimidine-6-carboxamideN-({4-[(3-ethoxy-4-fluorobenzene)sulfonyl]phenyl}methyl)thieno[2,3-0.0033 0.0031 c]pyridine-2-carboxamideN-({4-[(3-ethoxybenzene)sulfonyl]phenyl}methyl)-1H-pyrazolo[3,4- 0.01460.0190 b]pyridine-5-carboxamideN-({4-[(3-ethoxybenzene)sulfonyl]phenyl}methyl)-1H-pyrrolo[3,2- 0.00770.0035 c]pyridine-2-carboxamideN-({4-[(3-ethoxybenzene)sulfonyl]phenyl}methyl)furo[2,3-c]pyridine-2-0.0068 0.0110 carboxamideN-({4-[(3-ethoxybenzene)sulfonyl]phenyl}methyl)imidazo[1,2- 0.00500.0031 a]pyridine-6-carboxamideN-({4-[(3-ethoxybenzene)sulfonyl]phenyl}methyl)imidazo[1,2- 0.00210.0067 a]pyrimidine-6-carboxamideN-({4-[(3-ethoxybenzene)sulfonyl]phenyl}methyl)thieno[2,3- 0.0032 0.0029c]pyridine-2-carboxamideN-({4-[(3-ethylbenzene)sulfonyl]phenyl}methyl)-1H-pyrazolo[3,4- 0.00700.0071 b]pyridine-5-carboxamideN-({4-[(3-ethylbenzene)sulfonyl]phenyl}methyl)furo[2,3-c]pyridine-2-0.0087 0.0065 carboxamideN-({4-[(3-ethylbenzene)sulfonyl]phenyl}methyl)imidazo[1,2-a]pyridine-0.00483 0.00323 6-carboxamideN-({4-[(3-ethylbenzene)sulfonyl]phenyl}methyl)imidazo[1,2- 0.0038 0.0041a]pyrimidine-6-carboxamideN-({4-[(3-fluoro-2-methoxybenzene)sulfonyl]phenyl}methyl)-1H- 0.1210.1-1 pyrazolo[3,4-b]pyridine-5-carboxamideN-({4-[(3-fluoro-2-methoxybenzene)sulfonyl]phenyl}methyl)-1H- 0.03240.0063 pyrrolo[3,2-c]pyridine-2-carboxamideN-({4-[(3-fluoro-2-methoxybenzene)sulfonyl]phenyl}methyl)furo[2,3-0.0166 0.0309 c]pyridine-2-carboxamide N-({4-[(3-fluoro-2- 0.0769 0.0650methoxybenzene)sulfonyl]phenyl}methyl)imidazo[1,2-a]pyridine-6-carboxamide N-({4-[(3-fluoro-2- 0.0289 0.1-1methoxybenzene)sulfonyl]phenyl}methyl)imidazo[1,2-a]pyrimidine-6-carboxamideN-({4-[(3-fluoro-2-methoxybenzene)sulfonyl]phenyl}methyl)thieno[2,3-0.0133 0.0125 c]pyridine-2-carboxamideN-({4-[(3-fluoro-2-methylbenzene)sulfonyl]phenyl}methyl)-1H- 0.04690.0718 pyrazolo[3,4-b]pyridine-5-carboxamideN-({4-[(3-fluoro-2-methylbenzene)sulfonyl]phenyl}methyl)-1H- 0.05760.0132 pyrrolo[3,2-c]pyridine-2-carboxamideN-({4-[(3-fluoro-2-methylbenzene)sulfonyl]phenyl}methyl)furo[2,3- 0.01320.0307 c]pyridine-2-carboxamideN-({4-[(3-fluoro-2-methylbenzene)sulfonyl]phenyl}methyl)imidazo[1,2-0.0469 0.0132 a]pyridine-6-carboxamideN-({4-[(3-fluoro-2-methylbenzene)sulfonyl]phenyl}methyl)imidazo[1,2-0.0081 0.0656 a]pyrimidine-6-carboxamideN-({4-[(3-fluoro-2-methylbenzene)sulfonyl]phenyl}methyl)thieno[2,3-0.0071 0.0214 c]pyridine-2-carboxamideN-({4-[(3-fluoro-4-methoxybenzene)sulfonyl]phenyl}methyl)-1H- 0.04300.0060 pyrazolo[3,4-b]pyridine-5-carboxamideN-({4-[(3-fluoro-4-methoxybenzene)sulfonyl]phenyl}methyl)furo[2,3-0.0022 0.0068 c]pyridine-2-carboxamide N-({4-[(3-fluoro-4- 0.005950.00289 methoxybenzene)sulfonyl]phenyl}methyl)imidazo[1,2-a]pyridine-6-carboxamide N-({4-[(3-fluoro-4- 0.0017 0.0083methoxybenzene)sulfonyl]phenyl}methyl)imidazo[1,2-a]pyrimidine-6-carboxamide N-({4-[(3-fluoro-4-methylbenzene)sulfonyl]phenyl}methyl)-1H-0.0117 0.0056 pyrazolo[3,4-b]pyridine-5-carboxamideN-({4-[(3-fluoro-4-methylbenzene)sulfonyl]phenyl}methyl)furo[2,3- 0.01400.0033 c]pyridine-2-carboxamideN-({4-[(3-fluoro-4-methylbenzene)sulfonyl]phenyl}methyl)imidazo[1,2-0.0133 0.00378 a]pyridine-6-carboxamideN-({4-[(3-fluoro-4-methylbenzene)sulfonyl]phenyl}methyl)imidazo[1,2-0.0023 0.0063 a]pyrimidine-6-carboxamideN-({4-[(3-fluoro-4-propoxybenzene)sulfonyl]phenyl}methyl)-1H- 0.01160.0065 pyrazolo[3,4-b]pyridine-5-carboxamideN-({4-[(3-fluoro-4-propoxybenzene)sulfonyl]phenyl}methyl)-1H- 0.03090.0104 pyrrolo[3,2-c]pyridine-2-carboxamideN-({4-[(3-fluoro-4-propoxybenzene)sulfonyl]phenyl}methyl)furo[2,3-0.0068 0.0118 c]pyridine-2-carboxamide N-({4-[(3-fluoro-4- 0.0221 0.0044propoxybenzene)sulfonyl]phenyl}methyl)imidazo[1,2-a]pyridine-6-carboxamide N-({4-[(3-fluoro-4- 0.0027 0.0033propoxybenzene)sulfonyl]phenyl}methyl)imidazo[1,2-a]pyrimidine-6-carboxamideN-({4-[(3-fluoro-4-propoxybenzene)sulfonyl]phenyl}methyl)thieno[2,3-0.0037 0.0081 c]pyridine-2-carboxamideN-({4-[(3-fluoro-5-methoxybenzene)sulfonyl]phenyl}methyl)-1H- 0.00440.0063 pyrazolo[3,4-b]pyridine-5-carboxamideN-({4-[(3-fluoro-5-methoxybenzene)sulfonyl]phenyl}methyl)furo[2,3-0.0174 0.0033 c]pyridine-2-carboxamide N-({4-[(3-fluoro-5- 0.0016 0.0033methoxybenzene)sulfonyl]phenyl}methyl)imidazo[1,2-a]pyrimidine-6-carboxamide N-({4-[(3-fluoro-5-methylbenzene)sulfonyl]phenyl}methyl)-1H-0.0095 0.0056 pyrazolo[3,4-b]pyridine-5-carboxamideN-({4-[(3-fluoro-5-methylbenzene)sulfonyl]phenyl}methyl)-1H- 0.00830.0018 pyrrolo[3,2-c]pyridine-2-carboxamideN-({4-[(3-fluoro-5-methylbenzene)sulfonyl]phenyl}methyl)furo[2,3- 0.00340.0032 c]pyridine-2-carboxamideN-({4-[(3-fluoro-5-methylbenzene)sulfonyl]phenyl}methyl)imidazo[1,2-0.0027 0.0006 a]pyridine-6-carboxamideN-({4-[(3-fluoro-5-methylbenzene)sulfonyl]phenyl}methyl)imidazo[1,2-0.0015 0.0054 a]pyrimidine-6-carboxamideN-({4-[(3-fluoro-5-methylbenzene)sulfonyl]phenyl}methyl)thieno[2,3-0.0010 0.0006 c]pyridine-2-carboxamideN-({4-[(3-fluorobenzene)sulfonyl]phenyl}methyl)-1H-pyrazolo[3,4- 0.03390.0253 b]pyridine-5-carboxamideN-({4-[(3-fluorobenzene)sulfonyl]phenyl}methyl)furo[2,3-c]pyridine-2-0.0058 0.0145 carboxamideN-({4-[(3-fluorobenzene)sulfonyl]phenyl}methyl)imidazo[1,2- 0.02210.0122 a]pyridine-6-carboxamideN-({4-[(3-fluorobenzene)sulfonyl]phenyl}methyl)imidazo[1,2- 0.00190.0221 a]pyrimidine-6-carboxamideN-({4-[(3-hydroxybenzene)sulfonyl]phenyl}methyl)imidazo[1,2- 0.0050.0070 a]pyridine-6-carboxamideN-({4-[(3-methanesulfonylbenzene)sulfonyl]phenyl}methyl)furo[2,3- 0.00600.0068 c]pyridine-2-carboxamide N-({4-[(3- 0.0256 0.016methanesulfonylbenzene)sulfonyl]phenyl}methyl)imidazo[1,2-a]pyridine-6-carboxamideN-({4-[(3-methanesulfonylbenzene)sulfonyl]phenyl}methyl)thieno[2,3-0.0017 0.0035 c]pyridine-2-carboxamideN-({4-[(3-methoxy-4-methylbenzene)sulfonyl]phenyl}methyl)-1H- 0.00360.0034 pyrazolo[3,4-b]pyridine-5-carboxamideN-({4-[(3-methoxy-4-methylbenzene)sulfonyl]phenyl}methyl)-1H- 0.00790.0030 pyrrolo[3,2-c]pyridine-2-carboxamideN-({4-[(3-methoxy-4-methylbenzene)sulfonyl]phenyl}methyl)furo[2,3-0.0046 0.0031 c]pyridine-2-carboxamide N-({4-[(3-methoxy-4- 0.00130.0017 methylbenzene)sulfonyl]phenyl}methyl)imidazo[1,2-a]pyrimidine-6-carboxamide N-({4-[(3-methoxy-4- 0.0027 0.0015methylbenzene)sulfonyl]phenyl}methyl)thieno[2,3-c]pyridine-2-carboxamideN-({4-[(3-methoxy-5-methylbenzene)sulfonyl]phenyl}methyl)-1H- 0.00960.0028 pyrrolo[3,2-c]pyridine-2-carboxamideN-({4-[(3-methoxy-5-methylbenzene)sulfonyl]phenyl}methyl)furo[2,3-0.0022 0.0016 c]pyridine-2-carboxamide N-({4-[(3-methoxy-5- 0.00530.0016 methylbenzene)sulfonyl]phenyl}methyl)imidazo[1,2-a]pyridine-6-carboxamide N-({4-[(3-methoxy-5- 0.0016 0.0013methylbenzene)sulfonyl]phenyl}methyl)imidazo[1,2-a]pyrimidine-6-carboxamide N-({4-[(3-methoxy-5- 0.0024 0.0008methylbenzene)sulfonyl]phenyl}methyl)thieno[2,3-c]pyridine-2-carboxamideN-({4-[(3-methoxybenzene)sulfonyl]phenyl}methyl)-1H-pyrazolo[3,4- 0.02090.0100 b]pyridine-5-carboxamideN-({4-[(3-methoxybenzene)sulfonyl]phenyl}methyl)furo[2,3-c]pyridine-0.0035 0.0069 2-carboxamideN-({4-[(3-methoxybenzene)sulfonyl]phenyl}methyl)imidazo[1,2- 0.004970.00245 a]pyridine-6-carboxamideN-({4-[(3-methoxybenzene)sulfonyl]phenyl}methyl)imidazo[1,2- 0.00200.0124 a]pyrimidine-6-carboxamideN-({4-[(3-methylbenzene)sulfonyl]phenyl}methyl)furo[2,3-c]pyridine-2-0.0023 0.0053 carboxamideN-({4-[(3-methylbenzene)sulfonyl]phenyl}methyl)imidazo[1,2- 0.008120.00639 a]pyridine-6-carboxamideN-({4-[(3-methylbenzene)sulfonyl]phenyl}methyl)imidazo[1,2- 0.00190.0091 a]pyrimidine-6-carboxamideN-({4-[(3-phenylbenzene)sulfonyl]phenyl}methyl)-1,3-benzothiazole-6-0.0185   1-10 carboxamideN-({4-[(3-phenylbenzene)sulfonyl]phenyl}methyl)-1H-pyrrolo[3,2- 0.00230.0119 c]pyridine-2-carboxamideN-({4-[(3-phenylbenzene)sulfonyl]phenyl}methyl)furo[2,3-c]pyridine-2-0.0137 0.0234 carboxamideN-({4-[(3-phenylbenzene)sulfonyl]phenyl}methyl)imidazo[1,2- 0.01220.0068 a]pyridine-6-carboxamideN-({4-[(3-phenylbenzene)sulfonyl]phenyl}methyl)imidazo[1,2- 0.00090.0033 a]pyrimidine-6-carboxamideN-({4-[(3-phenylbenzene)sulfonyl]phenyl}methyl)thieno[2,3-c]pyridine-0.0045 0.0100 2-carboxamideN-({4-[(3-phenylpropane)sulfonyl]phenyl}methyl)-1H-pyrrolo[3,2- 0.0140.078 c]pyridine-2-carboxamideN-({4-[(3-propoxybenzene)sulfonyl]phenyl}methyl)-1H-pyrazolo[3,4- 0.03040.041 b]pyridine-5-carboxamideN-({4-[(3-propoxybenzene)sulfonyl]phenyl}methyl)-1H-pyrrolo[3,2- 0.01020.0122 c]pyridine-2-carboxamideN-({4-[(3-propoxybenzene)sulfonyl]phenyl}methyl)furo[2,3-c]pyridine-0.0101 0.0252 2-carboxamideN-({4-[(3-propoxybenzene)sulfonyl]phenyl}methyl)imidazo[1,2- 0.00420.0063 a]pyridine-6-carboxamideN-({4-[(3-propoxybenzene)sulfonyl]phenyl}methyl)imidazo[1,2- 0.00480.0075 a]pyrimidine-6-carboxamideN-({4-[(3-propoxybenzene)sulfonyl]phenyl}methyl)thieno[2,3- 0.00400.0122 c]pyridine-2-carboxamideN-({4-[(3-sulfamoylbenzene)sulfonyl]phenyl}methyl)-1H-pyrazolo[3,4-0.0301 0.1-1 b]pyridine-5-carboxamideN-({4-[(3-sulfamoylbenzene)sulfonyl]phenyl}methyl)imidazo[1,2- 0.01030.0546 a]pyridine-6-carboxamideN-({4-[(3-sulfamoylbenzene)sulfonyl]phenyl}methyl)thieno[2,3- 0.00200.0121 c]pyridine-2-carboxamideN-({4-[(3-tert-butylbenzene)sulfonyl]phenyl}methyl)furo[2,3- 0.00930.0070 c]pyridine-2-carboxamideN-({4-[(3-tert-butylbenzene)sulfonyl]phenyl}methyl)imidazo[1,2- 0.00970.0032 a]pyridine-6-carboxamideN-({4-[(3-tert-butylbenzene)sulfonyl]phenyl}methyl)imidazo[1,2- <0.000650.0012 a]pyrimidine-6-carboxamideN-({4-[(3-tert-butylbenzene)sulfonyl]phenyl}methyl)thieno[2,3- 0.01050.0091 c]pyridine-2-carboxamide N-({4-[(4,5-difluoro-2- 0.0281 0.0259methoxybenzene)sulfonyl]phenyl}methyl)furo[2,3-c]pyridine-2- carboxamideN-({4-[(4,5-difluoro-2- 0.0281 0.0068methoxybenzene)sulfonyl]phenyl}methyl)imidazo[1,2-a]pyridine-6-carboxamide N-({4-[(4,5-difluoro-2- 0.0119 0.0249methoxybenzene)sulfonyl]phenyl}methyl)imidazo[1,2-a]pyrimidine-6-carboxamideN-({4-[(4-acetylbenzene)sulfonyl]phenyl}methyl)-1H-pyrazolo[3,4- 0.02890.0037 b]pyridine-5-carboxamideN-({4-[(4-acetylbenzene)sulfonyl]phenyl}methyl)imidazo[1,2- 0.00520.0065 a]pyrimidine-6-carboxamideN-({4-[(4-butoxy-2-methylbenzene)sulfonyl]phenyl}methyl)-1H- 0.07090.0688 pyrazolo[3,4-b]pyridine-5-carboxamideN-({4-[(4-butoxy-2-methylbenzene)sulfonyl]phenyl}methyl)-1H- 0.08000.0625 pyrrolo[3,2-c]pyridine-2-carboxamideN-({4-[(4-butoxy-2-methylbenzene)sulfonyl]phenyl}methyl)furo[2,3- 0.01600.0648 c]pyridine-2-carboxamide N-({4-[(4-butoxy-2- 0.0100 0.0224methylbenzene)sulfonyl]phenyl}methyl)imidazo[1,2-a]pyridine-6-carboxamideN-({4-[(4-butoxy-2-methylbenzene)sulfonyl]phenyl}methyl)thieno[2,3-0.0033   1.0-0.1 c]pyridine-2-carboxamideN-({4-[(4-butoxy-3-chlorobenzene)sulfonyl]phenyl}methyl)-1H- 0.00450.0111 pyrazolo[3,4-b]pyridine-5-carboxamideN-({4-[(4-butoxy-3-chlorobenzene)sulfonyl]phenyl}methyl)-1H- 0.01780.0124 pyrrolo[3,2-c]pyridine-2-carboxamideN-({4-[(4-butoxy-3-chlorobenzene)sulfonyl]phenyl}methyl)furo[2,3- 0.00470.0100 c]pyridine-2-carboxamideN-({4-[(4-butoxy-3-chlorobenzene)sulfonyl]phenyl}methyl)imidazo[1,2-0.0041 0.0076 a]pyridine-6-carboxamideN-({4-[(4-butoxy-3-chlorobenzene)sulfonyl]phenyl}methyl)thieno[2,3-0.0048 0.0125 c]pyridine-2-carboxamideN-({4-[(4-butoxy-3-fluorobenzene)sulfonyl]phenyl}methyl)-1H- 0.05360.0134 pyrrolo[3,2-c]pyridine-2-carboxamideN-({4-[(4-butoxy-3-fluorobenzene)sulfonyl]phenyl}methyl)furo[2,3- 0.01230.0139 c]pyridine-2-carboxamideN-({4-[(4-butoxy-3-fluorobenzene)sulfonyl]phenyl}methyl)imidazo[1,2-0.0062 0.0031 a]pyridine-6-carboxamideN-({4-[(4-butoxy-3-fluorobenzene)sulfonyl]phenyl}methyl)imidazo[1,2-0.0012 0.0031 a]pyrimidine-6-carboxamideN-({4-[(4-butoxy-3-fluorobenzene)sulfonyl]phenyl}methyl)thieno[2,3-0.0047 0.0126 c]pyridine-2-carboxamideN-({4-[(4-butoxybenzene)sulfonyl]phenyl}methyl)-1H-pyrazolo[3,4- 0.02750.0225 b]pyridine-5-carboxamideN-({4-[(4-butoxybenzene)sulfonyl]phenyl}methyl)-1H-pyrrolo[3,2- 0.00840.0171 c]pyridine-2-carboxamideN-({4-[(4-butoxybenzene)sulfonyl]phenyl}methyl)furo[2,3-c]pyridine-2-0.0062 0.0130 carboxamideN-({4-[(4-butoxybenzene)sulfonyl]phenyl}methyl)imidazo[1,2- 0.00380.0028 a]pyridine-6-carboxamideN-({4-[(4-butoxybenzene)sulfonyl]phenyl}methyl)thieno[2,3- 0.0036 0.0103c]pyridine-2-carboxamideN-({4-[(4-butylbenzene)sulfonyl]phenyl}methyl)-1H-pyrazolo[3,4- 0.07120.0684 b]pyridine-5-carboxamideN-({4-[(4-butylbenzene)sulfonyl]phenyl}methyl)-1H-pyrrolo[3,2- 0.01460.0358 c]pyridine-2-carboxamideN-({4-[(4-butylbenzene)sulfonyl]phenyl}methyl)furo[2,3-c]pyridine-2-0.0181 0.0265 carboxamideN-({4-[(4-butylbenzene)sulfonyl]phenyl}methyl)imidazo[1,2-a]pyridine-0.0057 0.0076 6-carboxamideN-({4-[(4-butylbenzene)sulfonyl]phenyl}methyl)imidazo[1,2- 0.0053 0.0107a]pyrimidine-6-carboxamideN-({4-[(4-butylbenzene)sulfonyl]phenyl}methyl)thieno[2,3-c]pyridine-0.0029 0.0260 2-carboxamideN-({4-[(4-chloro-2-ethoxybenzene)sulfonyl]phenyl}methyl)-1H- 0.01120.0004 pyrrolo[3,2-c]pyridine-2-carboxamideN-({4-[(4-chloro-2-ethoxybenzene)sulfonyl]phenyl}methyl)furo[2,3- 0.00720.0051 c]pyridine-2-carboxamideN-({4-[(4-chloro-2-ethoxybenzene)sulfonyl]phenyl}methyl)imidazo[1,2-0.0041 0.0007 a]pyridine-6-carboxamideN-({4-[(4-chloro-2-ethoxybenzene)sulfonyl]phenyl}methyl)imidazo[1,2-0.0020 0.0045 a]pyrimidine-6-carboxamideN-({4-[(4-chloro-2-ethoxybenzene)sulfonyl]phenyl}methyl)thieno[2,3-0.0024 <0.0004 c]pyridine-2-carboxamideN-({4-[(4-chloro-2-methoxybenzene)sulfonyl]phenyl}methyl)furo[2,3-0.0085 0.0248 c]pyridine-2-carboxamide N-({4-[(4-chloro-2- 0.0187 0.0126methoxybenzene)sulfonyl]phenyl}methyl)imidazo[1,2-a]pyridine-6-carboxamide N-({4-[(4-chloro-2- 0.0033 0.0247methoxybenzene)sulfonyl]phenyl}methyl)imidazo[1,2-a]pyrimidine-6-carboxamide N-({4-[(4-chloro-2-methylbenzene)sulfonyl]phenyl}methyl)-1H-0.0775 0.0587 pyrazolo[3,4-b]pyridine-5-carboxamideN-({4-[(4-chloro-2-methylbenzene)sulfonyl]phenyl}methyl)furo[2,3- 0.02490.0647 c]pyridine-2-carboxamideN-({4-[(4-chloro-2-methylbenzene)sulfonyl]phenyl}methyl)imidazo[1,2-0.0066 0.0539 a]pyrimidine-6-carboxamideN-({4-[(4-chloro-3-fluorobenzene)sulfonyl]phenyl}methyl)furo[2,3- 0.01850.0065 c]pyridine-2-carboxamideN-({4-[(4-chloro-3-fluorobenzene)sulfonyl]phenyl}methyl)imidazo[1,2-0.00722 0.00724 a]pyridine-6-carboxamideN-({4-[(4-chloro-3-fluorobenzene)sulfonyl]phenyl}methyl)imidazo[1,2-0.0019 0.0089 a]pyrimidine-6-carboxamideN-({4-[(4-chloro-3-methoxybenzene)sulfonyl]phenyl}methyl)-1H- 0.01270.0130 pyrazolo[3,4-b]pyridine-5-carboxamideN-({4-[(4-chloro-3-methoxybenzene)sulfonyl]phenyl}methyl)-1H- 0.00550.0036 pyrrolo[3,2-c]pyridine-2-carboxamideN-({4-[(4-chloro-3-methoxybenzene)sulfonyl]phenyl}methyl)furo[2,3-0.0059 0.0060 c]pyridine-2-carboxamide N-({4-[(4-chloro-3- 0.0135 0.006methoxybenzene)sulfonyl]phenyl}methyl)imidazo[1,2-a]pyridine-6-carboxamide N-({4-[(4-chloro-3- 0.0027 0.0052methoxybenzene)sulfonyl]phenyl}methyl)imidazo[1,2-a]pyrimidine-6-carboxamide N-({4-[(4-chloro-3- 0.0026 0.0023methoxybenzene)sulfonyl]phenyl}methyl)thieno[2,3-c]pyridine-2-carboxamideN-({4-[(4-chlorobenzene)sulfonyl]phenyl}methyl)-1H-pyrazolo[3,4- 0.02880.022 b]pyridine-5-carboxamideN-({4-[(4-chlorobenzene)sulfonyl]phenyl}methyl)furo[2,3-c]pyridine-2-0.0049 0.0142 carboxamideN-({4-[(4-chlorobenzene)sulfonyl]phenyl}methyl)imidazo[1,2- 0.00250.0236 a]pyrimidine-6-carboxamideN-({4-[(4-cyanobenzene)sulfonyl]phenyl}methyl)-1H-pyrazolo[3,4- 0.02840.0208 b]pyridine-5-carboxamideN-({4-[(4-cyanobenzene)sulfonyl]phenyl}methyl)-1H-pyrrolo[3,2- 0.01110.0251 c]pyridine-2-carboxamideN-({4-[(4-cyanobenzene)sulfonyl]phenyl}methyl)furo[2,3-c]pyridine-2-0.0053 0.0309 carboxamideN-({4-[(4-cyanobenzene)sulfonyl]phenyl}methyl)imidazo[1,2- 0.0160 0.0141a]pyridine-6-carboxamideN-({4-[(4-cyclohexylbenzene)sulfonyl]phenyl}methyl)imidazo[1,2- 0.01780.0117 a]pyridine-6-carboxamideN-({4-[(4-cyclohexylbenzene)sulfonyl]phenyl}methyl)imidazo[1,2- 0.00580.0077 a]pyrimidine-6-carboxamideN-({4-[(4-cyclohexylbenzene)sulfonyl]phenyl}methyl)thieno[2,3- 0.00340.0129 c]pyridine-2-carboxamideN-({4-[(4-ethoxy-2-methylbenzene)sulfonyl]phenyl}methyl)-1H- 0.10830.0667 pyrazolo[3,4-b]pyridine-5-carboxamideN-({4-[(4-ethoxy-2-methylbenzene)sulfonyl]phenyl}methyl)-1H- 0.00920.0126 pyrrolo[3,2-c]pyridine-2-carboxamideN-({4-[(4-ethoxy-2-methylbenzene)sulfonyl]phenyl}methyl)furo[2,3- 0.02160.0274 c]pyridine-2-carboxamide N-({4-[(4-ethoxy-2- 0.0066 0.0111methylbenzene)sulfonyl]phenyl}methyl)imidazo[1,2-a]pyridine-6-carboxamide N-({4-[(4-ethoxy-2- 0.0117 0.0607methylbenzene)sulfonyl]phenyl}methyl)imidazo[1,2-a]pyrimidine-6-carboxamideN-({4-[(4-ethoxy-2-methylbenzene)sulfonyl]phenyl}methyl)thieno[2,3-0.0012 0.0132 c]pyridine-2-carboxamideN-({4-[(4-ethoxy-3-fluorobenzene)sulfonyl]phenyl}methyl)-1H- 0.00950.0052 pyrazolo[3,4-b]pyridine-5-carboxamideN-({4-[(4-ethoxy-3-fluorobenzene)sulfonyl]phenyl}methyl)-1H- 0.02050.0054 pyrrolo[3,2-c]pyridine-2-carboxamideN-({4-[(4-ethoxy-3-fluorobenzene)sulfonyl]phenyl}methyl)imidazo[1,2-0.0127 0.0018 a]pyridine-6-carboxamideN-({4-[(4-ethoxy-3-fluorobenzene)sulfonyl]phenyl}methyl)imidazo[1,2-0.0009 0.0031 a]pyrimidine-6-carboxamideN-({4-[(4-ethoxy-3-fluorobenzene)sulfonyl]phenyl}methyl)thieno[2,3-0.0089 0.0036 c]pyridine-2-carboxamideN-({4-[(4-ethoxybenzene)sulfonyl]phenyl}methyl)-1H-pyrazolo[3,4- 0.01510.0084 b]pyridine-5-carboxamideN-({4-[(4-ethoxybenzene)sulfonyl]phenyl}methyl)furo[2,3-c]pyridine-2-0.0025 0.0071 carboxamideN-({4-[(4-ethoxybenzene)sulfonyl]phenyl}methyl)imidazo[1,2- 0.00450.0029 a]pyridine-6-carboxamideN-({4-[(4-ethoxybenzene)sulfonyl]phenyl}methyl)imidazo[1,2- 0.00200.0061 a]pyrimidine-6-carboxamideN-({4-[(4-ethoxybenzene)sulfonyl]phenyl}methyl)thieno[2,3- 0.0021 0.0040c]pyridine-2-carboxamideN-({4-[(4-ethylbenzene)sulfonyl]phenyl}methyl)furo[2,3-c]pyridine-2-0.0050 0.007 carboxamideN-({4-[(4-ethylbenzene)sulfonyl]phenyl}methyl)imidazo[1,2-a]pyridine-0.0165 0.00736 6-carboxamideN-({4-[(4-ethylbenzene)sulfonyl]phenyl}methyl)imidazo[1,2- 0.0012 0.0062a]pyrimidine-6-carboxamideN-({4-[(4-fluoro-2,5-dimethylbenzene)sulfonyl]phenyl}methyl)-1H- 0.03730.0459 pyrazolo[3,4-b]pyridine-5-carboxamideN-({4-[(4-fluoro-2,5-dimethylbenzene)sulfonyl]phenyl}methyl)-1H- 0.05140.0128 pyrrolo[3,2-c]pyridine-2-carboxamideN-({4-[(4-fluoro-2,5-dimethylbenzene)sulfonyl]phenyl}methyl)furo[2,3-0.0176 0.0242 c]pyridine-2-carboxamide N-({4-[(4-fluoro-2,5- 0.04400.011 dimethylbenzene)sulfonyl]phenyl}methyl)imidazo[1,2-a]pyridine-6-carboxamide N-({4-[(4-fluoro-2,5- 0.0058 0.0294dimethylbenzene)sulfonyl]phenyl}methyl)imidazo[1,2-a]pyrimidine-6-carboxamide N-({4-[(4-fluoro-2,5- 0.0042 0.0136dimethylbenzene)sulfonyl]phenyl}methyl)thieno[2,3-c]pyridine-2-carboxamideN-({4-[(4-fluoro-2-methoxybenzene)sulfonyl]phenyl}methyl)-1H- 0.1590.0742 pyrazolo[3,4-b]pyridine-5-carboxamideN-({4-[(4-fluoro-2-methoxybenzene)sulfonyl]phenyl}methyl)furo[2,3-0.0127 0.0160 c]pyridine-2-carboxamide N-({4-[(4-fluoro-2- 0.01930.00705 methoxybenzene)sulfonyl]phenyl}methyl)imidazo[1,2-a]pyridine-6-carboxamide N-({4-[(4-fluoro-2- 0.0191 0.0736methoxybenzene)sulfonyl]phenyl}methyl)imidazo[1,2-a]pyrimidine-6-carboxamide N-({4-[(4-fluoro-2-methylbenzene)sulfonyl]phenyl}methyl)-1H-0.0788 0.0983 pyrazolo[3,4-b]pyridine-5-carboxamideN-({4-[(4-fluoro-2-methylbenzene)sulfonyl]phenyl}methyl)furo[2,3- 0.01870.0651 c]pyridine-2-carboxamideN-({4-[(4-fluoro-2-methylbenzene)sulfonyl]phenyl}methyl)imidazo[1,2-0.0130 0.1-1 a]pyrimidine-6-carboxamideN-({4-[(4-fluoro-3-methoxybenzene)sulfonyl]phenyl}methyl)-1H- 0.02390.0115 pyrazolo[3,4-b]pyridine-5-carboxamideN-({4-[(4-fluoro-3-methoxybenzene)sulfonyl]phenyl}methyl)-1H- 0.02780.0054 pyrrolo[3,2-c]pyridine-2-carboxamideN-({4-[(4-fluoro-3-methoxybenzene)sulfonyl]phenyl}methyl)furo[2,3-0.0078 0.0070 c]pyridine-2-carboxamide N-({4-[(4-fluoro-3- 0.0197 0.0067methoxybenzene)sulfonyl]phenyl}methyl)imidazo[1,2-a]pyridine-6-carboxamide N-({4-[(4-fluoro-3- 0.0049 0.0108methoxybenzene)sulfonyl]phenyl}methyl)imidazo[1,2-a]pyrimidine-6-carboxamideN-({4-[(4-fluoro-3-methoxybenzene)sulfonyl]phenyl}methyl)thieno[2,3-0.0090 0.0031 c]pyridine-2-carboxamideN-({4-[(4-fluoro-3-methylbenzene)sulfonyl]phenyl}methyl)-1H- 0.00500.0083 pyrazolo[3,4-b]pyridine-5-carboxamideN-({4-[(4-fluoro-3-methylbenzene)sulfonyl]phenyl}methyl)furo[2,3- 0.01320.006 c]pyridine-2-carboxamideN-({4-[(4-fluoro-3-methylbenzene)sulfonyl]phenyl}methyl)imidazo[1,2-0.0235 0.00714 a]pyridine-6-carboxamideN-({4-[(4-fluoro-3-methylbenzene)sulfonyl]phenyl}methyl)imidazo[1,2-0.0022 0.0096 a]pyrimidine-6-carboxamideN-({4-[(4-methanesulfonylbenzene)sulfonyl]phenyl}methyl)-1H- 0.02930.0238 pyrazolo[3,4-b]pyridine-5-carboxamide N-({4-[(4- 0.105 0.0247methanesulfonylbenzene)sulfonyl]phenyl}methyl)imidazo[1,2-a]pyridine-6-carboxamideN-({4-[(4-methoxy-2,5-dimethylbenzene)sulfonyl]phenyl}methyl)-1H- 0.03680.0236 pyrazolo[3,4-b]pyridine-5-carboxamide N-({4-[(4-methoxy-2,5-0.0123 0.0128dimethylbenzene)sulfonyl]phenyl}methyl)furo[2,3-c]pyridine-2-carboxamide N-({4-[(4-methoxy-2,5- 0.0281 0.006dimethylbenzene)sulfonyl]phenyl}methyl)imidazo[1,2-a]pyridine-6-carboxamide N-({4-[(4-methoxy-2,5- 0.0052 0.0130dimethylbenzene)sulfonyl]phenyl}methyl)imidazo[1,2-a]pyrimidine-6-carboxamideN-({4-[(4-methoxy-2-methylbenzene)sulfonyl]phenyl}methyl)-1H- 0.0290.0555 pyrazolo[3,4-b]pyridine-5-carboxamideN-({4-[(4-methoxy-2-methylbenzene)sulfonyl]phenyl}methyl)furo[2,3-0.0216 0.0351 c]pyridine-2-carboxamide N-({4-[(4-methoxy-2- 0.00240.0679 methylbenzene)sulfonyl]phenyl}methyl)imidazo[1,2-a]pyrimidine-6-carboxamideN-({4-[(4-methoxy-3,5-dimethylbenzene)sulfonyl]phenyl}methyl)-1H- 0.0050.00185 pyrazolo[3,4-b]pyridine-5-carboxamideN-({4-[(4-methoxy-3,5-dimethylbenzene)sulfonyl]phenyl}methyl)-1H- 0.05160.0017 pyrrolo[3,2-c]pyridine-2-carboxamide N-({4-[(4-methoxy-3,5-0.0056 0.0018dimethylbenzene)sulfonyl]phenyl}methyl)furo[2,3-c]pyridine-2-carboxamide N-({4-[(4-methoxy-3,5- 0.0146 0.0014dimethylbenzene)sulfonyl]phenyl}methyl)imidazo[1,2-a]pyridine-6-carboxamide N-({4-[(4-methoxy-3,5- 0.0027 0.0013dimethylbenzene)sulfonyl]phenyl}methyl)imidazo[1,2-a]pyrimidine-6-carboxamide N-({4-[(4-methoxy-3,5- 0.0098 0.0009dimethylbenzene)sulfonyl]phenyl}methyl)thieno[2,3-c]pyridine-2-carboxamide N-({4-[(4-methoxy-3- 0.0141 0.00532methylbenzene)sulfonyl]phenyl}methyl)imidazo[1,2-a]pyridine-6-carboxamide N-({4-[(4-methoxy-3- 0.0022 0.0055methylbenzene)sulfonyl]phenyl}methyl)imidazo[1,2-a]pyrimidine-6-carboxamideN-({4-[(4-methoxybenzene)sulfonyl]phenyl}methyl)-1H-pyrazolo[3,4- 0.02090.0143 b]pyridine-5-carboxamideN-({4-[(4-methoxybenzene)sulfonyl]phenyl}methyl)furo[2,3-c]pyridine-0.0055 0.006 2-carboxamideN-({4-[(4-methoxybenzene)sulfonyl]phenyl}methyl)imidazo[1,2- 0.009740.00866 a]pyridine-6-carboxamideN-({4-[(4-methoxybenzene)sulfonyl]phenyl}methyl)imidazo[1,2- 0.00270.0207 a]pyrimidine-6-carboxamideN-({4-[(4-methylbenzene)sulfonyl]phenyl}methyl)furo[2,3-c]pyridine-2-0.1208 0.006 carboxamideN-({4-[(4-methylbenzene)sulfonyl]phenyl}methyl)imidazo[1,2- 0.0176 0.012a]pyridine-6-carboxamideN-({4-[(4-methylbenzene)sulfonyl]phenyl}methyl)imidazo[1,2- 0.00430.0194 a]pyrimidine-6-carboxamideN-({4-[(4-phenylbenzene)sulfonyl]phenyl}methyl)-1,3-benzothiazole-6-0.0207 0.1-1 carboxamideN-({4-[(4-phenylbenzene)sulfonyl]phenyl}methyl)-1H-pyrazolo[3,4- 0.03200.0117 b]pyridine-5-carboxamideN-({4-[(4-phenylbenzene)sulfonyl]phenyl}methyl)-1H-pyrrolo[3,2- 0.03100.0133 c]pyridine-2-carboxamideN-({4-[(4-phenylbenzene)sulfonyl]phenyl}methyl)furo[2,3-c]pyridine-2-0.0037 0.0069 carboxamideN-({4-[(4-phenylbenzene)sulfonyl]phenyl}methyl)imidazo[1,2- 0.00320.0076 a]pyrimidine-6-carboxamideN-({4-[(4-phenylbenzene)sulfonyl]phenyl}methyl)thieno[2,3-c]pyridine-0.0030 0.0106 2-carboxamideN-({4-[(4-phenylbutane)sulfonyl]phenyl}methyl)-1H-pyrrolo[3,2- 0.2160.0715 c]pyridine-2-carboxamideN-({4-[(4-propoxybenzene)sulfonyl]phenyl}methyl)-1H-pyrrolo[3,2- 0.00530.0067 c]pyridine-2-carboxamideN-({4-[(4-propoxybenzene)sulfonyl]phenyl}methyl)furo[2,3-c]pyridine-0.0495 0.012 2-carboxamideN-({4-[(4-propoxybenzene)sulfonyl]phenyl}methyl)imidazo[1,2- 0.00610.0019 a]pyridine-6-carboxamideN-({4-[(4-propoxybenzene)sulfonyl]phenyl}methyl)imidazo[1,2- 0.00220.0061 a]pyrimidine-6-carboxamideN-({4-[(4-propoxybenzene)sulfonyl]phenyl}methyl)thieno[2,3- 0.00430.0081 c]pyridine-2-carboxamideN-({4-[(5-acetyl-2-methoxybenzene)sulfonyl]phenyl}methyl)-1H- 0.02770.0275 pyrazolo[3,4-b]pyridine-5-carboxamideN-({4-[(5-acetyl-2-methoxybenzene)sulfonyl]phenyl}methyl)furo[2,3-0.0072 0.0038 c]pyridine-2-carboxamide N-({4-[(5-acetyl-2- 0.0379 0.0127methoxybenzene)sulfonyl]phenyl}methyl)imidazo[1,2-a]pyridine-6-carboxamide N-({4-[(5-acetyl-2- 0.0172 0.0548methoxybenzene)sulfonyl]phenyl}methyl)imidazo[1,2-a]pyrimidine-6-carboxamideN-({4-[(5-chloro-2-ethoxybenzene)sulfonyl]phenyl}methyl)imidazo[1,2-0.0022 0.0005 a]pyridine-6-carboxamideN-({4-[(5-chloro-2-ethoxybenzene)sulfonyl]phenyl}methyl)imidazo[1,2-0.0019 0.0033 a]pyrimidine-6-carboxamideN-({4-[(5-chloro-2-ethoxybenzene)sulfonyl]phenyl}methyl)thieno[2,3-0.0027 0.0005 c]pyridine-2-carboxamide N-({4-[(5-chloro-2- 0.014 0.1682hydroxybenzene)sulfonyl]phenyl}methyl)imidazo[1,2-a]pyridine-6-carboxamideN-({4-[(5-chloro-2-methoxybenzene)sulfonyl]phenyl}methyl)-1H- 0.04920.0081 pyrazolo[3,4-b]pyridine-5-carboxamide N-({4-[(5-chloro-2- 0.01910.0032 methoxybenzene)sulfonyl]phenyl}methyl)imidazo[1,2-a]pyridine-6-carboxamide N-({4-[(5-chloro-2- 0.0055 0.0061methoxybenzene)sulfonyl]phenyl}methyl)imidazo[1,2-a]pyrimidine-6-carboxamide N-({4-[(5-chloro-2-methylbenzene)sulfonyl]phenyl}methyl)-1H-0.0227 0.0139 pyrazolo[3,4-b]pyridine-5-carboxamideN-({4-[(5-chloro-2-methylbenzene)sulfonyl]phenyl}methyl)furo[2,3- 0.00580.0078 c]pyridine-2-carboxamideN-({4-[(5-chloro-2-methylbenzene)sulfonyl]phenyl}methyl)imidazo[1,2-0.0019 0.0037 a]pyridine-6-carboxamideN-({4-[(5-chloro-2-methylbenzene)sulfonyl]phenyl}methyl)imidazo[1,2-0.0031 0.0043 a]pyrimidine-6-carboxamideN-({4-[(5-chloro-2-methylbenzene)sulfonyl]phenyl}methyl)thieno[2,3-0.0048 0.0066 c]pyridine-2-carboxamideN-({4-[(5-chloro-2-propoxybenzene)sulfonyl]phenyl}methyl)-1H- 0.04920.0251 pyrazolo[3,4-b]pyridine-5-carboxamideN-({4-[(5-chloro-2-propoxybenzene)sulfonyl]phenyl}methyl)-1H- 0.00750.0012 pyrrolo[3,2-c]pyridine-2-carboxamideN-({4-[(5-chloro-2-propoxybenzene)sulfonyl]phenyl}methyl)furo[2,3-0.0080 0.0093 c]pyridine-2-carboxamide N-({4-[(5-chloro-2- 0.0080 0.0032propoxybenzene)sulfonyl]phenyl}methyl)imidazo[1,2-a]pyridine-6-carboxamideN-({4-[(5-chloro-2-propoxybenzene)sulfonyl]phenyl}methyl)thieno[2,3-0.0057 0.0012 c]pyridine-2-carboxamide N-({4-[(5-cyano-2- 0.0146 0.0119methoxybenzene)sulfonyl]phenyl}methyl)imidazo[1,2-a]pyridine-6-carboxamideN-({4-[(5-fluoro-2-methoxybenzene)sulfonyl]phenyl}methyl)-1H- 0.03900.0151 pyrazolo[3,4-b]pyridine-5-carboxamideN-({4-[(5-fluoro-2-methoxybenzene)sulfonyl]phenyl}methyl)furo[2,3-0.0022 0.0124 c]pyridine-2-carboxamide N-({4-[(5-fluoro-2- 0.022 0.00665methoxybenzene)sulfonyl]phenyl}methyl)imidazo[1,2-a]pyridine-6-carboxamide N-({4-[(5-fluoro-2- 0.0073 0.0261methoxybenzene)sulfonyl]phenyl}methyl)imidazo[1,2-a]pyrimidine-6-carboxamideN-({4-[(5-fluoro-2-methoxybenzene)sulfonyl]phenyl}methyl)thieno[2,3-0.0020 0.0008 c]pyridine-2-carboxamideN-({4-[(5-fluoro-2-methylbenzene)sulfonyl]phenyl}methyl)-1H- 0.02040.0597 pyrazolo[3,4-b]pyridine-5-carboxamideN-({4-[(5-fluoro-2-methylbenzene)sulfonyl]phenyl}methyl)furo[2,3- 0.01430.0249 c]pyridine-2-carboxamideN-({4-[(5-fluoro-2-methylbenzene)sulfonyl]phenyl}methyl)imidazo[1,2-0.0126 0.0229 a]pyridine-6-carboxamideN-({4-[(5-fluoro-2-methylbenzene)sulfonyl]phenyl}methyl)imidazo[1,2-0.0027 0.0351 a]pyrimidine-6-carboxamideN-({4-[(5-tert-butyl-2-methoxybenzene)sulfonyl]phenyl}methyl)-1H- 0.04560.0216 pyrazolo[3,4-b]pyridine-5-carboxamide N-({4-[(5-tert-butyl-2-0.0218 0.0101methoxybenzene)sulfonyl]phenyl}methyl)furo[2,3-c]pyridine-2- carboxamideN-({4-[(5-tert-butyl-2- 0.029 0.00677methoxybenzene)sulfonyl]phenyl}methyl)imidazo[1,2-a]pyridine-6-carboxamide N-({4-[(5-tert-butyl-2- 0.0098 0.0077methoxybenzene)sulfonyl]phenyl}methyl)imidazo[1,2-a]pyrimidine-6-carboxamideN-({4-[(6-chloro-2-fluoro-3-methylbenzene)sulfonyl]phenyl}methyl)- 0.1120.1-1 1H-pyrazolo[3,4-b]pyridine-5-carboxamideN-({4-[(6-chloro-2-fluoro-3-methylbenzene)sulfonyl]phenyl}methyl)-0.0065 0.0071 1H-pyrrolo[3,2-c]pyridine-2-carboxamideN-({4-[(6-chloro-2-fluoro-3- 0.0219 0.0293methylbenzene)sulfonyl]phenyl}methyl)furo[2,3-c]pyridine-2- carboxamideN-({4-[(6-chloro-2-fluoro-3- 0.0077 0.0068methylbenzene)sulfonyl]phenyl}methyl)thieno[2,3-c]pyridine-2-carboxamideN-({4-[1-(3-chlorophenyl)-1H-pyrazole-4-sulfonyl]phenyl}methyl)-1H-0.0282 0.0556 pyrazolo[3,4-b]pyridine-5-carboxamideN-({4-[1-(3-chlorophenyl)-1H-pyrazole-4-sulfonyl]phenyl}methyl)-1H-0.0169 0.0131 pyrrolo[3,2-c]pyridine-2-carboxamideN-({4-[1-(3-chlorophenyl)-1H-pyrazole-4- 0.0116 0.0140sulfonyl]phenyl}methyl)furo[2,3-c]pyridine-2-carboxamideN-({4-[1-(3-chlorophenyl)-1H-pyrazole-4- 0.0140 0.0064sulfonyl]phenyl}methyl)imidazo[1,2-a]pyridine-6-carboxamideN-({4-[1-(3-chlorophenyl)-1H-pyrazole-4- 0.0022 0.0115sulfonyl]phenyl}methyl)imidazo[1,2-a]pyrimidine-6-carboxamideN-({4-[1-(3-chlorophenyl)-1H-pyrazole-4- 0.0041 0.0139sulfonyl]phenyl}methyl)thieno[2,3-c]pyridine-2-carboxamideN-({4-[1-(4-fluorophenyl)-1H-pyrazole-4-sulfonyl]phenyl}methyl)-1H-0.0184 0.0066 pyrrolo[3,2-c]pyridine-2-carboxamideN-({4-[1-(4-fluorophenyl)-1H-pyrazole-4- 0.0069 0.0074sulfonyl]phenyl}methyl)furo[2,3-c]pyridine-2-carboxamideN-({4-[1-(4-fluorophenyl)-1H-pyrazole-4- 0.0045 0.0062sulfonyl]phenyl}methyl)thieno[2,3-c]pyridine-2-carboxamideN-({4-[1-(propan-2-yl)-1H-pyrazole-4- 0.008 0.0027sulfonyl]phenyl}methyl)imidazo[1,2-a]pyridine-6-carboxamideN-({4-[1-methyl-3-(trifluoromethyl)-1H-pyrazole-4- 0.0299 0.0278sulfonyl]phenyl}methyl)imidazo[1,2-a]pyridine-6-carboxamideN-({4-[1-methyl-5-(trifluoromethyl)-1H-pyrazole-4- 0.0534 0.0434sulfonyl]phenyl}methyl)-1H-pyrazolo[3,4-b]pyridine-5-carboxamideN-({4-[1-methyl-5-(trifluoromethyl)-1H-pyrazole-4- 0.0040 0.0679sulfonyl]phenyl}methyl)imidazo[1,2-a]pyrimidine-6-carboxamideN-({4-[2-(3-fluorophenyl)-1,3-thiazole-4-sulfonyl]phenyl}methyl)-1H-0.0271 0.0609 pyrazolo[3,4-b]pyridine-5-carboxamideN-({4-[2-(3-fluorophenyl)-1,3-thiazole-4-sulfonyl]phenyl}methyl)-1H-0.0192 0.0232 pyrrolo[3,2-c]pyridine-2-carboxamideN-({4-[2-(3-fluorophenyl)-1,3-thiazole-4- 0.0119 0.0504sulfonyl]phenyl}methyl)furo[2,3-c]pyridine-2-carboxamideN-({4-[2-(3-fluorophenyl)-1,3-thiazole-4- 0.0229 0.0128sulfonyl]phenyl}methyl)imidazo[1,2-a]pyridine-6-carboxamideN-({4-[2-(3-fluorophenyl)-1,3-thiazole-4- 0.0010 0.0069sulfonyl]phenyl}methyl)imidazo[1,2-a]pyrimidine-6-carboxamideN-({4-[2-(3-fluorophenyl)-1,3-thiazole-4- 0.0066 0.0244sulfonyl]phenyl}methyl)thieno[2,3-c]pyridine-2-carboxamideN-({4-[2-(benzenesulfonyl)ethyl]phenyl}methyl)-1H-pyrrolo[3,2- 0.0230.166 c]pyridine-2-carboxamideN-({4-[2-(dimethylamino)pyrimidine-5-sulfonyl]phenyl}methyl)-1H- 0.00790.0059 pyrazolo[3,4-b]pyridine-5-carboxamideN-({4-[2-(dimethylamino)pyrimidine-5-sulfonyl]phenyl}methyl)-1H- 0.01900.0035 pyrrolo[3,2-c]pyridine-2-carboxamideN-({4-[2-(dimethylamino)pyrimidine-5- 0.0258 0.012sulfonyl]phenyl}methyl)furo[2,3-c]pyridine-2-carboxamideN-({4-[2-(dimethylamino)pyrimidine-5- 0.0229 0.0036sulfonyl]phenyl}methyl)imidazo[1,2-a]pyridine-6-carboxamideN-({4-[2-(dimethylamino)pyrimidine-5- 0.0080 0.0017sulfonyl]phenyl}methyl)thieno[2,3-c]pyridine-2-carboxamideN-({4-[2-(morpholin-4-yl)pyridine-3-sulfonyl]phenyl}methyl)furo[2,3-0.0325 0.0605 c]pyridine-2-carboxamideN-({4-[2-(morpholin-4-yl)pyridine-3- 0.0312 0.1-1sulfonyl]phenyl}methyl)imidazo[1,2-a]pyrimidine-6-carboxamideN-({4-[2-(pyrrolidin-1-yl)-1,3-thiazole-5-sulfonyl]phenyl}methyl)-1H-0.0028 0.0009 pyrazolo[3,4-b]pyridine-5-carboxamideN-({4-[2-(pyrrolidin-1-yl)-1,3-thiazole-5-sulfonyl]phenyl}methyl)-1H-0.0060 0.0005 pyrrolo[3,2-c]pyridine-2-carboxamideN-({4-[2-(pyrrolidin-1-yl)-1,3-thiazole-5- 0.0024 0.0004sulfonyl]phenyl}methyl)imidazo[1,2-a]pyridine-6-carboxamideN-({4-[2-(pyrrolidin-1-yl)-1,3-thiazole-5- 0.0029 0.0009sulfonyl]phenyl}methyl)imidazo[1,2-a]pyrimidine-6-carboxamideN-({4-[2-(pyrrolidin-1-yl)-1,3-thiazole-5- 0.0015 0.0007sulfonyl]phenyl}methyl)thieno[2,3-c]pyridine-2-carboxamideN-({4-[2-(trifluoromethyl)imidazo[1,2-a]pyridine-6- 0.0497 0.0330sulfonyl]phenyl}methyl)-1H-pyrazolo[3,4-b]pyridine-5-carboxamideN-({4-[2-(trifluoromethyl)imidazo[1,2-a]pyridine-6- 0.0212 0.0119sulfonyl]phenyl}methyl)furo[2,3-c]pyridine-2-carboxamideN-({4-[2-(trifluoromethyl)imidazo[1,2-a]pyridine-6- 0.0362 0.0070sulfonyl]phenyl}methyl)imidazo[1,2-a]pyridine-6-carboxamideN-({4-[2-(trifluoromethyl)imidazo[1,2-a]pyridine-6- 0.0031 0.0039sulfonyl]phenyl}methyl)thieno[2,3-c]pyridine-2-carboxamideN-({4-[2-(trifluoromethyl)pyridine-3-sulfonyl]phenyl}methyl)furo[2,3-0.0304 0.0279 c]pyridine-2-carboxamideN-({4-[3-chloro-2-(morpholin-4-yl)pyridine-4- 0.0085 0.0018sulfonyl]phenyl}methyl)thieno[2,3-c]pyridine-2-carboxamideN-({4-[4-(trifluoromethyl)pyridine-2-sulfonyl]phenyl}methyl)-1H- 0.02830.0118 pyrazolo[3,4-b]pyridine-5-carboxamideN-({4-[4-(trifluoromethyl)pyridine-2-sulfonyl]phenyl}methyl)furo[2,3-0.0139 0.0061 c]pyridine-2-carboxamideN-({4-[4-(trifluoromethyl)pyridine-2- 0.0197 0.0032sulfonyl]phenyl}methyl)imidazo[1,2-a]pyridine-6-carboxamideN-({4-[4-(trifluoromethyl)pyridine-2- 0.0087 0.0130sulfonyl]phenyl}methyl)imidazo[1,2-a]pyrimidine-6-carboxamideN-({4-[4-(trifluoromethyl)pyridine-2- 0.0036 0.0030sulfonyl]phenyl}methyl)thieno[2,3-c]pyridine-2-carboxamideN-({4-[5-(dimethylamino)pyrazine-2- 0.016 0.0036sulfonyl]phenyl}methyl)imidazo[1,2-a]pyridine-6-carboxamideN-({4-[5-(pyrrolidin-1-yl)pyridine-3-sulfonyl]phenyl}methyl)-1,3- 0.00920.1-1 benzothiazole-6-carboxamideN-({4-[5-(pyrrolidin-1-yl)pyridine-3-sulfonyl]phenyl}methyl)-1H- 0.01790.0040 pyrazolo[3,4-b]pyridine-5-carboxamideN-({4-[5-(pyrrolidin-1-yl)pyridine-3-sulfonyl]phenyl}methyl)-1H- 0.01390.0020 pyrrolo[3,2-c]pyridine-2-carboxamideN-({4-[5-(pyrrolidin-1-yl)pyridine-3-sulfonyl]phenyl}methyl)furo[2,3-0.0228 0.0049 c]pyridine-2-carboxamideN-({4-[5-(pyrrolidin-1-yl)pyridine-3- 0.004 0.0005sulfonyl]phenyl}methyl)imidazo[1,2-a]pyridine-6-carboxamideN-({4-[5-(trifluoromethyl)pyridine-2-sulfonyl]phenyl}methyl)-1H- 0.1-10.1-1 pyrazolo[3,4-b]pyridine-5-carboxamideN-({4-[5-(trifluoromethyl)pyridine-2-sulfonyl]phenyl}methyl)furo[2,3-0.0370 0.1-1 c]pyridine-2-carboxamideN-({4-[5-(trifluoromethyl)pyridine-2- 0.0463 0.0326sulfonyl]phenyl}methyl)imidazo[1,2-a]pyridine-6-carboxamideN-({4-[5-(trifluoromethyl)pyridine-2- 0.0059 0.0708sulfonyl]phenyl}methyl)imidazo[1,2-a]pyrimidine-6-carboxamideN-({4-[5-(trifluoromethyl)pyridine-2- 0.0235 0.1-1sulfonyl]phenyl}methyl)thieno[2,3-c]pyridine-2-carboxamideN-({4-[5-(trifluoromethyl)pyridine-3-sulfonyl]phenyl}methyl)-1H- 0.0110.004 pyrazolo[3,4-b]pyridine-5-carboxamideN-({4-[5-(trifluoromethyl)pyridine-3- 0.009 0.0013sulfonyl]phenyl}methyl)imidazo[1,2-a]pyridine-6-carboxamideN-({4-[6-(1H-pyrazol-1-yl)pyridine-3- 0.004 0.0019sulfonyl]phenyl}methyl)imidazo[1,2-a]pyridine-6-carboxamideN-({4-[6-(3,4-difluorophenyl)pyridine-2-sulfonyl]phenyl}methyl)-1H-0.0178 0.0410 pyrazolo[3,4-b]pyridine-5-carboxamideN-({4-[6-(3,4-difluorophenyl)pyridine-2-sulfonyl]phenyl}methyl)-1H-0.0160 0.0127 pyrrolo[3,2-c]pyridine-2-carboxamideN-({4-[6-(3,4-difluorophenyl)pyridine-2- 0.0050 0.0427sulfonyl]phenyl}methyl)furo[2,3-c]pyridine-2-carboxamideN-({4-[6-(3,4-difluorophenyl)pyridine-2- 0.0043 0.0057sulfonyl]phenyl}methyl)imidazo[1,2-a]pyridine-6-carboxamideN-({4-[6-(3,4-difluorophenyl)pyridine-2- 0.0022 0.0132sulfonyl]phenyl}methyl)thieno[2,3-c]pyridine-2-carboxamideN-({4-[6-(4-methylpiperazin-1-yl)pyridine-3-sulfonyl]phenyl}methyl)-0.006 0.0006 1H-pyrrolo[3,2-c]pyridine-2-carboxamideN-({4-[6-(dimethylamino)pyridine-3-sulfonyl]phenyl}methyl)-1H- 0.03050.0033 pyrazolo[3,4-b]pyridine-5-carboxamideN-({4-[6-(dimethylamino)pyridine-3-sulfonyl]phenyl}methyl)-1H- 0.02090.0034 pyrrolo[3,2-c]pyridine-2-carboxamideN-({4-[6-(dimethylamino)pyridine-3-sulfonyl]phenyl}methyl)furo[2,3-0.003 0.0018 c]pyridine-2-carboxamideN-({4-[6-(dimethylamino)pyridine-3- 0.0449 0.0027sulfonyl]phenyl}methyl)imidazo[1,2-a]pyridine-6-carboxamideN-({4-[6-(dimethylamino)pyridine-3- 0.0027 0.0059sulfonyl]phenyl}methyl)imidazo[1,2-a]pyrimidine-6-carboxamideN-({4-[6-(dimethylamino)pyridine-3- 0.001 0.0006sulfonyl]phenyl}methyl)thieno[2,3-c]pyridine-2-carboxamideN-({4-[6-(morpholin-4-yl)pyridine-3-sulfonyl]phenyl}methyl)-1H- 0.00570.0032 pyrazolo[3,4-b]pyridine-5-carboxamideN-({4-[6-(morpholin-4-yl)pyridine-3-sulfonyl]phenyl}methyl)-1H- 0.00960.0015 pyrrolo[3,2-c]pyridine-2-carboxamideN-({4-[6-(morpholin-4-yl)pyridine-3-sulfonyl]phenyl}methyl)furo[2,3-0.002 0.0009 c]pyridine-2-carboxamideN-({4-[6-(morpholin-4-yl)pyridine-3- 0.0090 0.0015sulfonyl]phenyl}methyl)imidazo[1,2-a]pyridine-6-carboxamideN-({4-[6-(morpholin-4-yl)pyridine-3- 0.0011 0.0033sulfonyl]phenyl}methyl)imidazo[1,2-a]pyrimidine-6-carboxamideN-({4-[6-(morpholin-4-yl)pyridine-3-sulfonyl]phenyl}methyl)thieno[2,3-0.0041 0.0007 c]pyridine-2-carboxamideN-({4-[6-(trifluoromethyl)pyridine-2-sulfonyl]phenyl}methyl)-1H- 0.02420.0111 pyrazolo[3,4-b]pyridine-5-carboxamideN-({4-[6-(trifluoromethyl)pyridine-2-sulfonyl]phenyl}methyl)furo[2,3-0.0050 0.0031 c]pyridine-2-carboxamideN-({4-[6-(trifluoromethyl)pyridine-2- 0.0087 0.0015sulfonyl]phenyl}methyl)imidazo[1,2-a]pyridine-6-carboxamideN-({4-[6-(trifluoromethyl)pyridine-2- 0.0114 0.0204sulfonyl]phenyl}methyl)imidazo[1,2-a]pyrimidine-6-carboxamideN-({4-[6-(trifluoromethyl)pyridine-2- 0.0021 0.0022sulfonyl]phenyl}methyl)thieno[2,3-c]pyridine-2-carboxamideN-({4-[6-(trifluoromethyl)pyridine-3- 0.0076 0.0067sulfonyl]phenyl}methyl)thieno[2,3-c]pyridine-2-carboxamideN-(1,3-benzothiazol-6-ylmethyl)-4-[(3- 0.0100 >10chlorobenzene)sulfonyl]benzamide N-[(4-{[2-(2,2,2-trifluoroethoxy)-4-0.009 0.0010(trifluoromethyl)benzene]sulfonyl}phenyl)methyl]-1H-pyrrolo[3,2-c]pyridine-2-carboxamide N-[(4-{[2-(2,2,2-trifluoroethoxy)-4- 0.0070.0012 (trifluoromethyl)benzene]sulfonyl}phenyl)methyl]imidazo[1,2-a]pyridine-6-carboxamide N-[(4-{[2-(benzyloxy)-5- 0.1-1 0.1-1(trifluoromethyl)benzene]sulfonyl}phenyl)methyl]-1H-pyrazolo[3,4-b]pyridine-5-carboxamide N-[(4-{[2-(benzyloxy)-5- 0.1303 0.0259(trifluoromethyl)benzene]sulfonyl}phenyl)methyl]-1H-pyrrolo[3,2-c]pyridine-2-carboxamide N-[(4-{[2-(benzyloxy)-5- 0.0332 0.1-1(trifluoromethyl)benzene]sulfonyl}phenyl)methyl]imidazo[1,2-a]pyrimidine-6-carboxamideN-[(4-{[2-(dimethylcarbamoyl)benzene]sulfonyl}phenyl)methyl]-1H- 0.1-10.1-1 pyrrolo[3,2-c]pyridine-2-carboxamide N-[(4-{[2- 0.1-1   1-10(dimethylcarbamoyl)benzene]sulfonyl}phenyl)methyl]furo[2,3-c]pyridine-2-carboxamide N-[(4-{[2- >0.1667 0.1-1(dimethylcarbamoyl)benzene]sulfonyl}phenyl)methyl]imidazo[1,2-a]pyridine-6-carboxamide N-[(4-{[2- 0.1-1   1-10(dimethylcarbamoyl)benzene]sulfonyl}phenyl)methyl]imidazo[1,2-a]pyrimidine-6-carboxamide N-[(4-{[2- 0.1-1 0.1-1(dimethylcarbamoyl)benzene]sulfonyl}phenyl)methyl]thieno[2,3-c]pyridine-2-carboxamideN-[(4-{[2-(ethoxymethyl)benzene]sulfonyl}phenyl)methyl]-1H- 0.05200.0612 pyrazolo[3,4-b]pyridine-5-carboxamideN-[(4-{[2-(ethoxymethyl)benzene]sulfonyl}phenyl)methyl]-1H- 0.01850.0067 pyrrolo[3,2-c]pyridine-2-carboxamideN-[(4-{[2-(ethoxymethyl)benzene]sulfonyl}phenyl)methyl]furo[2,3- 0.01330.0260 c]pyridine-2-carboxamideN-[(4-{[2-(ethoxymethyl)benzene]sulfonyl}phenyl)methyl]imidazo[1,2-0.0037 0.0396 a]pyrimidine-6-carboxamideN-[(4-{[2-(methylsulfamoyl)benzene]sulfonyl}phenyl)methyl]-1H- >0.167 >10pyrazolo[3,4-b]pyridine-5-carboxamideN-[(4-{[2-(methylsulfamoyl)benzene]sulfonyl}phenyl)methyl]furo[2,3-0.0513 0.0740 c]pyridine-2-carboxamide N-[(4-{[2- 0.0304   1-10(methylsulfamoyl)benzene]sulfonyl}phenyl)methyl]imidazo[1,2-a]pyrimidine-6-carboxamideN-[(4-{[2-(morpholin-4-ylmethyl)benzene]sulfonyl}phenyl)methyl]-1H-0.0694 0.0465 pyrazolo[3,4-b]pyridine-5-carboxamideN-[(4-{[2-(morpholin-4- 0.136 0.0342ylmethyl)benzene]sulfonyl}phenyl)methyl]imidazo[1,2-a]pyridine-6-carboxamide N-[(4-{[2-(morpholin-4- 0.0145 0.1-1ylmethyl)benzene]sulfonyl}phenyl)methyl]imidazo[1,2-a]pyrimidine-6-carboxamideN-[(4-{[2-(trifluoromethoxy)benzene]sulfonyl}phenyl)methyl]furo[2,3-0.0086 0.0146 c]pyridine-2-carboxamide N-[(4-{[2- 0.0024 0.0115(trifluoromethoxy)benzene]sulfonyl}phenyl)methyl]imidazo[1,2-a]pyrimidine-6-carboxamideN-[(4-{[2-(trifluoromethyl)benzene]sulfonyl}phenyl)methyl]furo[2,3-0.0194 0.0593 c]pyridine-2-carboxamide N-[(4-{[2- 0.0341 0.0579(trifluoromethyl)benzene]sulfonyl}phenyl)methyl]imidazo[1,2-a]pyridine-6-carboxamide N-[(4-{[2- 0.0100 0.1-1(trifluoromethyl)benzene]sulfonyl}phenyl)methyl]imidazo[1,2-a]pyrimidine-6-carboxamideN-[(4-{[2,4-bis(trifluoromethyl)benzene]sulfonyl}phenyl)methyl]-1H-0.0816 0.0562 pyrazolo[3,4-b]pyridine-5-carboxamideN-[(4-{[2,4-bis(trifluoromethyl)benzene]sulfonyl}phenyl)methyl]-1H-0.0401 0.0140 pyrrolo[3,2-c]pyridine-2-carboxamide N-[(4-{[2,4- 0.05300.0637 bis(trifluoromethyl)benzene]sulfonyl}phenyl)methyl]furo[2,3-c]pyridine-2-carboxamide N-[(4-{[2,4- 0.2202 0.0532bis(trifluoromethyl)benzene]sulfonyl}phenyl)methyl]imidazo[1,2-a]pyridine-6-carboxamide N-[(4-{[2,4- 0.0188 0.0964bis(trifluoromethyl)benzene]sulfonyl}phenyl)methyl]imidazo[1,2-a]pyrimidine-6-carboxamide N-[(4-{[2,4- 0.0215 0.0043bis(trifluoromethyl)benzene]sulfonyl}phenyl)methyl]thieno[2,3-c]pyridine-2-carboxamideN-[(4-{[2-chloro-3-(trifluoromethyl)benzene]sulfonyl}phenyl)methyl]-0.0365 0.0384 1H-pyrazolo[3,4-b]pyridine-5-carboxamideN-[(4-{[2-chloro-3-(trifluoromethyl)benzene]sulfonyl}phenyl)methyl]-0.0364 0.0088 1H-pyrrolo[3,2-c]pyridine-2-carboxamideN-[(4-{[2-chloro-3- 0.0184 0.0279(trifluoromethyl)benzene]sulfonyl}phenyl)methyl]furo[2,3-c]pyridine-2-carboxamide N-[(4-{[2-chloro-3- 0.0024 0.0246(trifluoromethyl)benzene]sulfonyl}phenyl)methyl]imidazo[1,2-a]pyrimidine-6-carboxamideN-[(4-{[2-chloro-4-(trifluoromethyl)benzene]sulfonyl}phenyl)methyl]-0.114 0.0869 1H-pyrazolo[3,4-b]pyridine-5-carboxamideN-[(4-{[2-chloro-4-(trifluoromethyl)benzene]sulfonyl}phenyl)methyl]-0.1269 0.0254 1H-pyrrolo[3,2-c]pyridine-2-carboxamideN-[(4-{[2-chloro-4- 0.0184 0.0644(trifluoromethyl)benzene]sulfonyl}phenyl)methyl]imidazo[1,2-a]pyrimidine-6-carboxamideN-[(4-{[2-chloro-5-(hydroxymethyl)benzene]sulfonyl}phenyl)methyl]-0.0083 0.0262 1H-pyrrolo[3,2-c]pyridine-2-carboxamideN-[(4-{[2-chloro-5-(trifluoromethoxy)benzene]sulfonyl}phenyl)methyl]-0.0531 0.0120 1H-pyrrolo[3,2-c]pyridine-2-carboxamideN-[(4-{[2-chloro-5- 0.0080 0.0125(trifluoromethoxy)benzene]sulfonyl}phenyl)methyl]imidazo[1,2-a]pyrimidine-6-carboxamide N-[(4-{[2-chloro-5- 0.0139 0.0141(trifluoromethyl)benzene]sulfonyl}phenyl)methyl]furo[2,3-c]pyridine-2-carboxamide N-[(4-{[2-chloro-5- 0.0070 0.0141(trifluoromethyl)benzene]sulfonyl}phenyl)methyl]imidazo[1,2-a]pyrimidine-6-carboxamide N-[(4-{[2-fluoro-3-(propan-2- 0.0078 0.0040yloxy)benzene]sulfonyl}phenyl)methyl]imidazo[1,2-a]pyridine-6-carboxamide N-[(4-{[2-fluoro-3-(propan-2- 0.0018 0.0070yloxy)benzene]sulfonyl}phenyl)methyl]imidazo[1,2-a]pyrimidine-6-carboxamide N-[(4-{[2-fluoro-3-(propan-2- 0.0047 0.0066yloxy)benzene]sulfonyl}phenyl)methyl]thieno[2,3-c]pyridine-2-carboxamide N-[(4-{[2-fluoro-3- 0.0098 0.0133(trifluoromethoxy)benzene]sulfonyl}phenyl)methyl]thieno[2,3-c]pyridine-2-carboxamideN-[(4-{[2-fluoro-4-(1H-pyrazol-1-yl)benzene]sulfonyl}phenyl)methyl]-0.0389 0.0344 1H-pyrazolo[3,4-b]pyridine-5-carboxamideN-[(4-{[2-fluoro-4-(1H-pyrazol-1- 0.0184 0.008yl)benzene]sulfonyl}phenyl)methyl]furo[2,3-c]pyridine-2-carboxamideN-[(4-{[2-fluoro-4-(1H-pyrazol-1- 0.00844 0.0128yl)benzene]sulfonyl}phenyl)methyl]imidazo[1,2-a]pyridine-6- carboxamideN-[(4-{[2-fluoro-4-(1H-pyrazol-1- 0.0022 0.0190yl)benzene]sulfonyl}phenyl)methyl]imidazo[1,2-a]pyrimidine-6-carboxamideN-[(4-{[2-fluoro-4-(trifluoromethyl)benzene]sulfonyl}phenyl)methyl]-0.0802 0.0281 1H-pyrrolo[3,2-c]pyridine-2-carboxamideN-[(4-{[2-fluoro-4- 0.0156 0.0157(trifluoromethyl)benzene]sulfonyl}phenyl)methyl]imidazo[1,2-a]pyridine-6-carboxamide N-[(4-{[2-fluoro-4- 0.0202 0.0423(trifluoromethyl)benzene]sulfonyl}phenyl)methyl]thieno[2,3-c]pyridine-2-carboxamide N-[(4-{[2-methoxy-3- 0.0219 0.0148(trifluoromethyl)benzene]sulfonyl}phenyl)methyl]imidazo[1,2-a]pyridine-6-carboxamide N-[(4-{[2-methoxy-3- 0.0094 0.0128(trifluoromethyl)benzene]sulfonyl}phenyl)methyl]thieno[2,3-c]pyridine-2-carboxamide N-[(4-{[2-methoxy-4-(1H-pyrazol-1- 0.02420.0094 yl)benzene]sulfonyl}phenyl)methyl]-1H-pyrazolo[3,4-b]pyridine-5-carboxamide N-[(4-{[2-methoxy-4-(1H-pyrazol-1- 0.0065 0.006yl)benzene]sulfonyl}phenyl)methyl]furo[2,3-c]pyridine-2-carboxamideN-[(4-{[2-methoxy-4-(1H-pyrazol-1- 0.021 0.00359yl)benzene]sulfonyl}phenyl)methyl]imidazo[1,2-a]pyridine-6- carboxamideN-[(4-{[2-methoxy-4-(1H-pyrazol-1- 0.0032 0.0087yl)benzene]sulfonyl}phenyl)methyl]imidazo[1,2-a]pyrimidine-6-carboxamide N-[(4-{[2-methoxy-4- 0.1200 0.0281(trifluoromethyl)benzene]sulfonyl}phenyl)methyl]-1H-pyrazolo[3,4-b]pyridine-5-carboxamide N-[(4-{[2-methoxy-4- 0.0264 0.00984(trifluoromethyl)benzene]sulfonyl}phenyl)methyl]imidazo[1,2-a]pyridine-6-carboxamide N-[(4-{[2-methoxy-4- 0.0044 0.0224(trifluoromethyl)benzene]sulfonyl}phenyl)methyl]imidazo[1,2-a]pyrimidine-6-carboxamide N-[(4-{[2-methoxy-4- 0.01 0.0022(trifluoromethyl)benzene]sulfonyl}phenyl)methyl]thieno[2,3-c]pyridine-2-carboxamideN-[(4-{[2-methoxy-5-(propan-2-yl)benzene]sulfonyl}phenyl)methyl]- 0.08920.0294 1H-pyrazolo[3,4-b]pyridine-5-carboxamideN-[(4-{[2-methoxy-5-(propan-2- 0.0154 0.0124yl)benzene]sulfonyl}phenyl)methyl]furo[2,3-c]pyridine-2-carboxamideN-[(4-{[2-methoxy-5-(propan-2- 0.0352 0.0064yl)benzene]sulfonyl}phenyl)methyl]imidazo[1,2-a]pyridine-6- carboxamideN-[(4-{[2-methoxy-5- 0.0926 0.0246(trifluoromethoxy)benzene]sulfonyl}phenyl)methyl]-1H-pyrazolo[3,4-b]pyridine-5-carboxamide N-[(4-{[2-methoxy-5- 0.0481 0.0066(trifluoromethoxy)benzene]sulfonyl}phenyl)methyl]-1H-pyrrolo[3,2-c]pyridine-2-carboxamide N-[(4-{[2-methoxy-5- 0.0677 0.0144(trifluoromethoxy)benzene]sulfonyl}phenyl)methyl]imidazo[1,2-a]pyridine-6-carboxamide N-[(4-{[2-methoxy-5- <0.00065 0.0058(trifluoromethoxy)benzene]sulfonyl}phenyl)methyl]imidazo[1,2-a]pyrimidine-6-carboxamide N-[(4-{[2-methoxy-5- 0.0068 0.0036(trifluoromethyl)benzene]sulfonyl}phenyl)methyl]imidazo[1,2-a]pyrimidine-6-carboxamideN-[(4-{[2-methyl-4-(1H-pyrazol-1-yl)benzene]sulfonyl}phenyl)methyl]-0.0271 0.0235 1H-pyrazolo[3,4-b]pyridine-5-carboxamideN-[(4-{[2-methyl-4-(1H-pyrazol-1- 0.0062 0.006yl)benzene]sulfonyl}phenyl)methyl]furo[2,3-c]pyridine-2-carboxamideN-[(4-{[2-methyl-4-(1H-pyrazol-1- 0.00799 0.0036yl)benzene]sulfonyl}phenyl)methyl]imidazo[1,2-a]pyridine-6- carboxamideN-[(4-{[2-methyl-4-(1H-pyrazol-1- 0.0015 0.0031yl)benzene]sulfonyl}phenyl)methyl]thieno[2,3-c]pyridine-2- carboxamideN-[(4-{[2-methyl-4-(trifluoromethyl)benzene]sulfonyl}phenyl)methyl]-0.1-1 0.0746 1H-pyrazolo[3,4-b]pyridine-5-carboxamideN-[(4-{[2-methyl-4-(trifluoromethyl)benzene]sulfonyl}phenyl)methyl]-0.0305 0.0253 1H-pyrrolo[3,2-c]pyridine-2-carboxamideN-[(4-{[2-methyl-4- 0.0345 0.0631(trifluoromethyl)benzene]sulfonyl}phenyl)methyl]furo[2,3-c]pyridine-2-carboxamide N-[(4-{[2-methyl-4- 0.0247 0.0166(trifluoromethyl)benzene]sulfonyl}phenyl)methyl]imidazo[1,2-a]pyridine-6-carboxamide N-[(4-{[2-methyl-4- 0.0071 0.0511(trifluoromethyl)benzene]sulfonyl}phenyl)methyl]imidazo[1,2-a]pyrimidine-6-carboxamide N-[(4-{[2-methyl-4- 0.0103 0.0242(trifluoromethyl)benzene]sulfonyl}phenyl)methyl]thieno[2,3-c]pyridine-2-carboxamideN-[(4-{[3-(1H-pyrazol-1-yl)benzene]sulfonyl}phenyl)methyl]-1H- 0.00970.0074 pyrrolo[3,2-c]pyridine-2-carboxamideN-[(4-{[3-(1H-pyrazol-1-yl)benzene]sulfonyl}phenyl)methyl]furo[2,3-0.0075 0.0091 c]pyridine-2-carboxamide N-[(4-{[3-(1H-pyrazol-1- 0.00480.0062 yl)benzene]sulfonyl}phenyl)methyl]imidazo[1,2-a]pyridine-6-carboxamideN-[(4-{[3-(1H-pyrazol-1-yl)benzene]sulfonyl}phenyl)methyl]thieno[2,3-0.0015 0.0001 c]pyridine-2-carboxamide N-[(4-{[3-(2,2,2- 0.0072 0.0120trifluoroethoxy)benzene]sulfonyl}phenyl)methyl]furo[2,3-c]pyridine-2-carboxamide N-[(4-{[3-(2,2,2- 0.0150 0.0059trifluoroethoxy)benzene]sulfonyl}phenyl)methyl]imidazo[1,2-a]pyridine-6-carboxamide N-[(4-{[3-(2,2,2- 0.0055 0.0114trifluoroethoxy)benzene]sulfonyl}phenyl)methyl]imidazo[1,2-a]pyrimidine-6-carboxamideN-[(4-{[3-(2-methylpropoxy)benzene]sulfonyl}phenyl)methyl]-1H- 0.02850.0342 pyrazolo[3,4-b]pyridine-5-carboxamideN-[(4-{[3-(2-methylpropoxy)benzene]sulfonyl}phenyl)methyl]-1H- 0.03220.0143 pyrrolo[3,2-c]pyridine-2-carboxamideN-[(4-{[3-(2-methylpropoxy)benzene]sulfonyl}phenyl)methyl]furo[2,3-0.0148 0.0677 c]pyridine-2-carboxamide N-[(4-{[3-(2- 0.0157 0.0106methylpropoxy)benzene]sulfonyl}phenyl)methyl]imidazo[1,2-a]pyridine-6-carboxamide N-[(4-{[3-(2- 0.0039 0.0132methylpropoxy)benzene]sulfonyl}phenyl)methyl]imidazo[1,2-a]pyrimidine-6-carboxamide N-[(4-{[3-(2- 0.0032 0.0252methylpropoxy)benzene]sulfonyl}phenyl)methyl]thieno[2,3-c]pyridine-2-carboxamide N-[(4-{[3-(3,5-dimethyl-1H-pyrazol-1- 0.0179 0.1-1yl)benzene]sulfonyl}phenyl)methyl]-1,3-benzothiazole-6-carboxamideN-[(4-{[3-(3,5-dimethyl-1H-pyrazol-1- 0.0253 0.0053yl)benzene]sulfonyl}phenyl)methyl]-1H-pyrazolo[3,4-b]pyridine-5-carboxamide N-[(4-{[3-(3,5-dimethyl-1H-pyrazol-1- 0.0132 0.0016yl)benzene]sulfonyl}phenyl)methyl]-1H-pyrrolo[3,2-c]pyridine-2-carboxamide N-[(4-{[3-(3,5-dimethyl-1H-pyrazol-1- 0.1-1 0.1-1yl)benzene]sulfonyl}phenyl)methyl]-5-hydroxy-1H-indole-2- carboxamideN-[(4-{[3-(3,5-dimethyl-1H-pyrazol-1- 0.0071 0.0035yl)benzene]sulfonyl}phenyl)methyl]furo[2,3-c]pyridine-2-carboxamideN-[(4-{[3-(3,5-dimethyl-1H-pyrazol-1- 0.0072 0.0008yl)benzene]sulfonyl}phenyl)methyl]imidazo[1,2-a]pyridine-6- carboxamideN-[(4-{[3-(3,5-dimethyl-1H-pyrazol-1- 0.0018 0.0041yl)benzene]sulfonyl}phenyl)methyl]imidazo[1,2-a]pyrimidine-6-carboxamide N-[(4-{[3-(3,5-dimethyl-1H-pyrazol-1- 0.0031 0.0015yl)benzene]sulfonyl}phenyl)methyl]thieno[2,3-c]pyridine-2- carboxamideN-[(4-{[3-(4- 0.0151 0.0340fluorophenoxy)benzene]sulfonyl}phenyl)methyl]imidazo[1,2-a]pyridine-6-carboxamide N-[(4-{[3-(4- 0.0026 0.0656fluorophenoxy)benzene]sulfonyl}phenyl)methyl]thieno[2,3-c]pyridine-2-carboxamide N-[(4-{[3-(5-methyl-1,2,4-oxadiazol-3- 0.0079 0.0032yl)benzene]sulfonyl}phenyl)methyl]furo[2,3-c]pyridine-2-carboxamideN-[(4-{[3-(5-methyl-1,2,4-oxadiazol-3- 0.0028 0.0023yl)benzene]sulfonyl}phenyl)methyl]imidazo[1,2-a]pyrimidine-6-carboxamide N-[(4-{[3-(5-methyl-1,2,4-oxadiazol-3- 0.0033 0.0010yl)benzene]sulfonyl}phenyl)methyl]thieno[2,3-c]pyridine-2- carboxamideN-[(4-{[3-(cyclopentylcarbamoyl)benzene]sulfonyl}phenyl)methyl]-1H-0.0333 0.033 pyrazolo[3,4-b]pyridine-5-carboxamide N-[(4-{[3- 0.00660.0226 (cyclopentylcarbamoyl)benzene]sulfonyl}phenyl)methyl]furo[2,3-c]pyridine-2-carboxamide N-[(4-{[3- 0.0103 0.0162(cyclopentylcarbamoyl)benzene]sulfonyl}phenyl)methyl]imidazo[1,2-a]pyridine-6-carboxamide N-[(4-{[3- 0.0047 0.0483(cyclopentylcarbamoyl)benzene]sulfonyl}phenyl)methyl]imidazo[1,2-a]pyrimidine-6-carboxamide N-[(4-{[3- 0.0048 0.0138(cyclopentylcarbamoyl)benzene]sulfonyl}phenyl)methyl]thieno[2,3-c]pyridine-2-carboxamideN-[(4-{[3-(diethylcarbamoyl)-5-fluorobenzene]sulfonyl}phenyl)methyl]-0.0093 0.0033 1H-pyrrolo[3,2-c]pyridine-2-carboxamideN-[(4-{[3-(diethylcarbamoyl)-5- 0.0103 0.0038fluorobenzene]sulfonyl}phenyl)methyl]furo[2,3-c]pyridine-2- carboxamideN-[(4-{[3-(diethylcarbamoyl)-5- 0.0047 0.0168fluorobenzene]sulfonyl}phenyl)methyl]imidazo[1,2-a]pyrimidine-6-carboxamideN-[(4-{[3-(difluoromethoxy)benzene]sulfonyl}phenyl)methyl]furo[2,3-0.0028 0.0030 c]pyridine-2-carboxamide N-[(4-{[3- 0.0021 0.0050(difluoromethoxy)benzene]sulfonyl}phenyl)methyl]imidazo[1,2-a]pyrimidine-6-carboxamide N-[(4-{[3- 0.0020 0.0032(dimethylsulfamoyl)benzene]sulfonyl}phenyl)methyl]furo[2,3-c]pyridine-2-carboxamide N-[(4-{[3- 0.0020 0.0112(dimethylsulfamoyl)benzene]sulfonyl}phenyl)methyl]imidazo[1,2-a]pyrimidine-6-carboxamideN-[(4-{[3-(ethanesulfonyl)benzene]sulfonyl}phenyl)methyl]-1H- 0.01700.0155 pyrrolo[3,2-c]pyridine-2-carboxamideN-[(4-{[3-(ethanesulfonyl)benzene]sulfonyl}phenyl)methyl]furo[2,3-0.0027 0.0032 c]pyridine-2-carboxamide N-[(4-{[3- 0.0135 0.0060(ethanesulfonyl)benzene]sulfonyl}phenyl)methyl]imidazo[1,2-a]pyridine-6-carboxamide N-[(4-{[3- 0.0027 0.0645(ethanesulfonyl)benzene]sulfonyl}phenyl)methyl]imidazo[1,2-a]pyrimidine-6-carboxamideN-[(4-{[3-(ethanesulfonyl)benzene]sulfonyl}phenyl)methyl]thieno[2,3-0.0028 0.0054 c]pyridine-2-carboxamideN-[(4-{[3-(ethylcarbamoyl)benzene]sulfonyl}phenyl)methyl]furo[2,3-0.0060 0.0064 c]pyridine-2-carboxamide N-[(4-{[3- 0.0031 0.0655(ethylcarbamoyl)benzene]sulfonyl}phenyl)methyl]imidazo[1,2-a]pyrimidine-6-carboxamideN-[(4-{[3-(methoxymethyl)benzene]sulfonyl}phenyl)methyl]-1H- 0.03870.0394 pyrazolo[3,4-b]pyridine-5-carboxamideN-[(4-{[3-(methoxymethyl)benzene]sulfonyl}phenyl)methyl]-1H- 0.02020.0128 pyrrolo[3,2-c]pyridine-2-carboxamideN-[(4-{[3-(methoxymethyl)benzene]sulfonyl}phenyl)methyl]furo[2,3- 0.01850.0134 c]pyridine-2-carboxamide N-[(4-{[3- 0.0067 0.0068(methoxymethyl)benzene]sulfonyl}phenyl)methyl]imidazo[1,2-a]pyridine-6-carboxamide N-[(4-{[3- 0.0032 0.0138(methoxymethyl)benzene]sulfonyl}phenyl)methyl]imidazo[1,2-a]pyrimidine-6-carboxamideN-[(4-{[3-(methoxymethyl)benzene]sulfonyl}phenyl)methyl]thieno[2,3-0.0026 0.0067 c]pyridine-2-carboxamideN-[(4-{[3-(methylcarbamoyl)benzene]sulfonyl}phenyl)methyl]furo[2,3-0.0081 0.0143 c]pyridine-2-carboxamide N-[(4-{[3- 0.0037 0.1-1(methylcarbamoyl)benzene]sulfonyl}phenyl)methyl]imidazo[1,2-a]pyrimidine-6-carboxamideN-[(4-{[3-(morpholin-4-yl)benzene]sulfonyl}phenyl)methyl]-1,3- 0.0401  1-10 benzothiazole-6-carboxamideN-[(4-{[3-(morpholin-4-yl)benzene]sulfonyl}phenyl)methyl]-1H- 0.01670.0130 pyrazolo[3,4-b]pyridine-5-carboxamideN-[(4-{[3-(morpholin-4-yl)benzene]sulfonyl}phenyl)methyl]-1H- 0.02070.0106 pyrrolo[3,2-c]pyridine-2-carboxamideN-[(4-{[3-(morpholin-4-yl)benzene]sulfonyl}phenyl)methyl]-1H- 0.00840.0017 pyrrolo[3,2-c]pyridine-2-carboxamideN-[(4-{[3-(morpholin-4-yl)benzene]sulfonyl}phenyl)methyl]furo[2,3-0.0050 0.0056 c]pyridine-2-carboxamide N-[(4-{[3-(morpholin-4- 0.00770.0033 yl)benzene]sulfonyl}phenyl)methyl]imidazo[1,2-a]pyridine-6-carboxamide N-[(4-{[3-(morpholin-4- 0.0027 0.0135yl)benzene]sulfonyl}phenyl)methyl]imidazo[1,2-a]pyrimidine-6-carboxamideN-[(4-{[3-(morpholin-4-yl)benzene]sulfonyl}phenyl)methyl]thieno[2,3-0.0040 0.0019 c]pyridine-2-carboxamideN-[(4-{[3-(morpholin-4-yl)benzene]sulfonyl}phenyl)methyl]thieno[2,3-0.0036 0.0032 c]pyridine-2-carboxamideN-[(4-{[3-(piperidin-1-yl)benzene]sulfonyl}phenyl)methyl]-1,3- 0.02100.1-1 benzothiazole-6-carboxamideN-[(4-{[3-(piperidin-1-yl)benzene]sulfonyl}phenyl)methyl]-1H- 0.05360.0140 pyrazolo[3,4-b]pyridine-5-carboxamideN-[(4-{[3-(piperidin-1-yl)benzene]sulfonyl}phenyl)methyl]-1H- 0.01440.0033 pyrrolo[3,2-c]pyridine-2-carboxamideN-[(4-{[3-(piperidin-1-yl)benzene]sulfonyl}phenyl)methyl]furo[2,3-0.0113 0.0127 c]pyridine-2-carboxamideN-[(4-{[3-(piperidin-1-yl)benzene]sulfonyl}phenyl)methyl]imidazo[1,2-0.0114 0.0034 a]pyridine-6-carboxamideN-[(4-{[3-(piperidin-1-yl)benzene]sulfonyl}phenyl)methyl]imidazo[1,2-0.0051 0.0114 a]pyrimidine-6-carboxamideN-[(4-{[3-(piperidin-1-yl)benzene]sulfonyl}phenyl)methyl]imidazo[1,2-0.0012 0.0057 a]pyrimidine-6-carboxamideN-[(4-{[3-(piperidin-1-yl)benzene]sulfonyl}phenyl)methyl]thieno[2,3-0.0167 0.0136 c]pyridine-2-carboxamide N-[(4-{[3-(piperidin-1- 0.00910.0035 ylmethyl)benzene]sulfonyl}phenyl)methyl]imidazo[1,2-a]pyridine-6-carboxamide N-[(4-{[3-(piperidin-1- 0.0019 0.0306ylmethyl)benzene]sulfonyl}phenyl)methyl]imidazo[1,2-a]pyrimidine-6-carboxamide N-[(4-{[3-(propan-2-yl)benzene]sulfonyl}phenyl)methyl]-1H-0.0139 0.0063 pyrazolo[3,4-b]pyridine-5-carboxamideN-[(4-{[3-(propan-2-yl)benzene]sulfonyl}phenyl)methyl]furo[2,3- 0.00450.007 c]pyridine-2-carboxamideN-[(4-{[3-(propan-2-yl)benzene]sulfonyl}phenyl)methyl]imidazo[1,2-0.0124 0.00349 a]pyridine-6-carboxamideN-[(4-{[3-(propan-2-yl)benzene]sulfonyl}phenyl)methyl]imidazo[1,2-0.0029 0.0053 a]pyrimidine-6-carboxamideN-[(4-{[3-(propan-2-yloxy)benzene]sulfonyl}phenyl)methyl]-1H- 0.04610.0245 pyrazolo[3,4-b]pyridine-5-carboxamideN-[(4-{[3-(propan-2-yloxy)benzene]sulfonyl}phenyl)methyl]furo[2,3-0.0126 0.0144 c]pyridine-2-carboxamide N-[(4-{[3-(propan-2- 0.00230.0105 yloxy)benzene]sulfonyl}phenyl)methyl]imidazo[1,2-a]pyrimidine-6-carboxamide N-[(4-{[3-(propane-1- 0.0023 0.0862sulfonamido)benzene]sulfonyl}phenyl)methyl]imidazo[1,2-a]pyrimidine-6-carboxamide N-[(4-{[3-(propane-1- 0.0015 0.0032sulfonamido)benzene]sulfonyl}phenyl)methyl]thieno[2,3-c]pyridine-2-carboxamideN-[(4-{[3-(pyrimidin-2-yl)benzene]sulfonyl}phenyl)methyl]imidazo[1,2-0.0219 0.0038 a]pyridine-6-carboxamideN-[(4-{[3-(pyrimidin-2-yl)benzene]sulfonyl}phenyl)methyl]imidazo[1,2-0.0032 0.0130 a]pyrimidine-6-carboxamideN-[(4-{[3-(pyrrolidin-1-yl)benzene]sulfonyl}phenyl)methyl]-1,3- 0.0088  1-10 benzothiazole-6-carboxamideN-[(4-{[3-(pyrrolidin-1-yl)benzene]sulfonyl}phenyl)methyl]-1H- 0.01710.0128 pyrazolo[3,4-b]pyridine-5-carboxamideN-[(4-{[3-(pyrrolidin-1-yl)benzene]sulfonyl}phenyl)methyl]-1H- 0.01340.0028 pyrrolo[3,2-c]pyridine-2-carboxamideN-[(4-{[3-(pyrrolidin-1-yl)benzene]sulfonyl}phenyl)methyl]furo[2,3-0.0082 0.0074 c]pyridine-2-carboxamideN-[(4-{[3-(pyrrolidin-1-yl)benzene]sulfonyl}phenyl)methyl]imidazo[1,2-0.0136 0.0016 a]pyridine-6-carboxamideN-[(4-{[3-(pyrrolidin-1-yl)benzene]sulfonyl}phenyl)methyl]imidazo[1,2-0.0025 0.0041 a]pyrimidine-6-carboxamideN-[(4-{[3-(pyrrolidin-1-yl)benzene]sulfonyl}phenyl)methyl]thieno[2,3-0.0019 0.0025 c]pyridine-2-carboxamideN-[(4-{[3-(trifluoromethoxy)benzene]sulfonyl}phenyl)methyl]-1H- 0.02040.0071 pyrazolo[3,4-b]pyridine-5-carboxamideN-[(4-{[3-(trifluoromethoxy)benzene]sulfonyl}phenyl)methyl]furo[2,3-0.0034 0.0067 c]pyridine-2-carboxamide N-[(4-{[3- 0.00873 0.00318(trifluoromethoxy)benzene]sulfonyl}phenyl)methyl]imidazo[1,2-a]pyridine-6-carboxamide N-[(4-{[3- 0.0025 0.0027(trifluoromethoxy)benzene]sulfonyl}phenyl)methyl]imidazo[1,2-a]pyrimidine-6-carboxamideN-[(4-{[3-(trifluoromethyl)benzene]sulfonyl}phenyl)methyl]-1,3- 0.0060.5481 benzothiazole-6-carboxamideN-[(4-{[3-(trifluoromethyl)benzene]sulfonyl}phenyl)methyl]-1H- 0.06070.0104 pyrazolo[3,4-b]pyridine-5-carboxamideN-[(4-{[3-(trifluoromethyl)benzene]sulfonyl}phenyl)methyl]furo[2,3-0.0054 0.0048 c]pyridine-2-carboxamide N-[(4-{[3- 0.00842 0.00172(trifluoromethyl)benzene]sulfonyl}phenyl)methyl]imidazo[1,2-a]pyridine-6-carboxamide N-[(4-{[3- 0.0027 0.0030(trifluoromethyl)benzene]sulfonyl}phenyl)methyl]imidazo[1,2-a]pyrimidine-6-carboxamideN-[(4-{[3-chloro-4-(trifluoromethyl)benzene]sulfonyl}phenyl)methyl]-0.0843 0.0264 1H-pyrazolo[3,4-b]pyridine-5-carboxamideN-[(4-{[3-chloro-4-(trifluoromethyl)benzene]sulfonyl}phenyl)methyl]-0.0133 0.0077 1H-pyrrolo[3,2-c]pyridine-2-carboxamideN-[(4-{[3-chloro-4- 0.0079 0.0062(trifluoromethyl)benzene]sulfonyl}phenyl)methyl]furo[2,3-c]pyridine-2-carboxamide N-[(4-{[3-chloro-4- 0.0029 0.0012(trifluoromethyl)benzene]sulfonyl}phenyl)methyl]imidazo[1,2-a]pyridine-6-carboxamide N-[(4-{[3-chloro-4- 0.0028 0.0018(trifluoromethyl)benzene]sulfonyl}phenyl)methyl]imidazo[1,2-a]pyrimidine-6-carboxamide N-[(4-{[3-chloro-4- 0.0030 0.0023(trifluoromethyl)benzene]sulfonyl}phenyl)methyl]thieno[2,3-c]pyridine-2-carboxamide N-[(4-{[3-chloro-5- 0.0084 0.0017(diethylcarbamoyl)benzene]sulfonyl}phenyl)methyl]furo[2,3-c]pyridine-2-carboxamide N-[(4-{[3-chloro-5- 0.0009 0.0012(diethylcarbamoyl)benzene]sulfonyl}phenyl)methyl]imidazo[1,2-a]pyrimidine-6-carboxamide N-[(4-{[3-chloro-5- 0.0023 0.0008(diethylcarbamoyl)benzene]sulfonyl}phenyl)methyl]thieno[2,3-c]pyridine-2-carboxamide N-[(4-{[3-chloro-5- 0.0058 0.0014(hydroxymethyl)benzene]sulfonyl}phenyl)methyl]imidazo[1,2-a]pyridine-6-carboxamide N-[(4-{[3-chloro-5- 0.0034 0.0114(hydroxymethyl)benzene]sulfonyl}phenyl)methyl]imidazo[1,2-a]pyrimidine-6-carboxamide N-[(4-{[3-chloro-5- 0.0033 0.0008(hydroxymethyl)benzene]sulfonyl}phenyl)methyl]thieno[2,3-c]pyridine-2-carboxamideN-[(4-{[3-chloro-5-(trifluoromethyl)benzene]sulfonyl}phenyl)methyl]-0.0078 0.00273 1H-pyrazolo[3,4-b]pyridine-5-carboxamideN-[(4-{[3-chloro-5-(trifluoromethyl)benzene]sulfonyl}phenyl)methyl]-0.0199 0.0027 1H-pyrrolo[3,2-c]pyridine-2-carboxamideN-[(4-{[3-chloro-5- 0.0044 0.0004(trifluoromethyl)benzene]sulfonyl}phenyl)methyl]imidazo[1,2-a]pyrimidine-6-carboxamideN-[(4-{[3-fluoro-4-(1H-pyrazol-1-yl)benzene]sulfonyl}phenyl)methyl]-0.0131 0.0033 1H-pyrazolo[3,4-b]pyridine-5-carboxamideN-[(4-{[3-fluoro-4-(1H-pyrazol-1- 0.0173 0.005yl)benzene]sulfonyl}phenyl)methyl]furo[2,3-c]pyridine-2-carboxamideN-[(4-{[3-fluoro-4-(1H-pyrazol-1- 0.00537 0.00341yl)benzene]sulfonyl}phenyl)methyl]imidazo[1,2-a]pyridine-6- carboxamideN-[(4-{[3-fluoro-4-(2,2,2- 0.0103 0.0223trifluoroethoxy)benzene]sulfonyl}phenyl)methyl]-1H-pyrazolo[3,4-b]pyridine-5-carboxamide N-[(4-{[3-fluoro-4-(2,2,2- 0.0069 0.0238trifluoroethoxy)benzene]sulfonyl}phenyl)methyl]furo[2,3-c]pyridine-2-carboxamide N-[(4-{[3-fluoro-4-(2,2,2- 0.0150 0.008trifluoroethoxy)benzene]sulfonyl}phenyl)methyl]imidazo[1,2-a]pyridine-6-carboxamide N-[(4-{[3-fluoro-4-(2,2,2- 0.0044 0.0073trifluoroethoxy)benzene]sulfonyl}phenyl)methyl]imidazo[1,2-a]pyrimidine-6-carboxamide N-[(4-{[3-fluoro-4-(2,2,2- 0.0046 0.0235trifluoroethoxy)benzene]sulfonyl}phenyl)methyl]thieno[2,3-c]pyridine-2-carboxamide N-[(4-{[3-fluoro-4- 0.0123 0.0112(methylsulfanyl)benzene]sulfonyl}phenyl)methyl]furo[2,3-c]pyridine-2-carboxamide N-[(4-{[3-fluoro-4- 0.0056 0.0027(methylsulfanyl)benzene]sulfonyl}phenyl)methyl]imidazo[1,2-a]pyridine-6-carboxamide N-[(4-{[3-fluoro-4- 0.0022 0.0020(methylsulfanyl)benzene]sulfonyl}phenyl)methyl]thieno[2,3-c]pyridine-2-carboxamideN-[(4-{[3-fluoro-4-(trifluoromethoxy)benzene]sulfonyl}phenyl)methyl]-0.0174 0.0137 1H-pyrazolo[3,4-b]pyridine-5-carboxamideN-[(4-{[3-fluoro-4-(trifluoromethoxy)benzene]sulfonyl}phenyl)methyl]-0.0262 0.0205 1H-pyrrolo[3,2-c]pyridine-2-carboxamideN-[(4-{[3-fluoro-4- 0.0100 0.0156(trifluoromethoxy)benzene]sulfonyl}phenyl)methyl]furo[2,3-c]pyridine-2-carboxamide N-[(4-{[3-fluoro-4- 0.0084 0.0063(trifluoromethoxy)benzene]sulfonyl}phenyl)methyl]imidazo[1,2-a]pyridine-6-carboxamide N-[(4-{[3-fluoro-4- 0.0040 0.0118(trifluoromethoxy)benzene]sulfonyl}phenyl)methyl]imidazo[1,2-a]pyrimidine-6-carboxamide N-[(4-{[3-fluoro-4- 0.0115 0.0115(trifluoromethoxy)benzene]sulfonyl}phenyl)methyl]thieno[2,3-c]pyridine-2-carboxamideN-[(4-{[3-fluoro-4-(trifluoromethyl)benzene]sulfonyl}phenyl)methyl]-0.0103 0.0130 1H-pyrrolo[3,2-c]pyridine-2-carboxamideN-[(4-{[3-fluoro-4- 0.0092 0.0137(trifluoromethyl)benzene]sulfonyl}phenyl)methyl]furo[2,3-c]pyridine-2-carboxamide N-[(4-{[3-fluoro-4- 0.0402 0.0044(trifluoromethyl)benzene]sulfonyl}phenyl)methyl]imidazo[1,2-a]pyridine-6-carboxamide N-[(4-{[3-fluoro-4- 0.0041 0.0069(trifluoromethyl)benzene]sulfonyl}phenyl)methyl]imidazo[1,2-a]pyrimidine-6-carboxamide N-[(4-{[3-fluoro-4- 0.0088 0.0072(trifluoromethyl)benzene]sulfonyl}phenyl)methyl]thieno[2,3-c]pyridine-2-carboxamide N-[(4-{[3-fluoro-5-(2,2,2- 0.008 0.00482trifluoroethoxy)benzene]sulfonyl}phenyl)methyl]-1H-pyrazolo[3,4-b]pyridine-5-carboxamide N-[(4-{[3-fluoro-5-(2,2,2- 0.0056 0.0019trifluoroethoxy)benzene]sulfonyl}phenyl)methyl]-1H-pyrrolo[3,2-c]pyridine-2-carboxamide N-[(4-{[3-fluoro-5-(2,2,2- 0.0074 0.0061trifluoroethoxy)benzene]sulfonyl}phenyl)methyl]furo[2,3-c]pyridine-2-carboxamide N-[(4-{[3-fluoro-5-(2,2,2- 0.0019 0.0015trifluoroethoxy)benzene]sulfonyl}phenyl)methyl]imidazo[1,2-a]pyrimidine-6-carboxamide N-[(4-{[3-fluoro-5-(2,2,2- 0.0029 0.0035trifluoroethoxy)benzene]sulfonyl}phenyl)methyl]thieno[2,3-c]pyridine-2-carboxamideN-[(4-{[3-fluoro-5-(2-methylpropoxy)benzene]sulfonyl}phenyl)methyl]-0.0112 0.00949 1H-pyrazolo[3,4-b]pyridine-5-carboxamideN-[(4-{[3-fluoro-5-(2-methylpropoxy)benzene]sulfonyl}phenyl)methyl]-0.0132 0.0070 1H-pyrrolo[3,2-c]pyridine-2-carboxamideN-[(4-{[3-fluoro-5-(2- 0.0103 0.0129methylpropoxy)benzene]sulfonyl}phenyl)methyl]furo[2,3-c]pyridine-2-carboxamide N-[(4-{[3-fluoro-5-(2- 0.0113 0.003methylpropoxy)benzene]sulfonyl}phenyl)methyl]imidazo[1,2-a]pyridine-6-carboxamide N-[(4-{[3-fluoro-5-(2- 0.0031 0.0034methylpropoxy)benzene]sulfonyl}phenyl)methyl]imidazo[1,2-a]pyrimidine-6-carboxamide N-[(4-{[3-fluoro-5-(2- 0.0048 0.0075methylpropoxy)benzene]sulfonyl}phenyl)methyl]thieno[2,3-c]pyridine-2-carboxamideN-[(4-{[3-fluoro-5-(morpholin-4-yl)benzene]sulfonyl}phenyl)methyl]-0.004 0.0008 1H-pyrrolo[3,2-c]pyridine-2-carboxamideN-[(4-{[3-fluoro-5-(morpholin-4- 0.003 0.0006yl)benzene]sulfonyl}phenyl)methyl]imidazo[1,2-a]pyridine-6- carboxamideN-[(4-{[3-fluoro-5-(pyrrolidin-1- 0.0039 0.0022yl)benzene]sulfonyl}phenyl)methyl]imidazo[1,2-a]pyridine-6- carboxamideN-[(4-{[3-fluoro-5-(pyrrolidin-1- 0.0031 0.0020yl)benzene]sulfonyl}phenyl)methyl]imidazo[1,2-a]pyrimidine-6-carboxamide N-[(4-{[3-fluoro-5-(pyrrolidin-1- 0.0012 0.0027yl)benzene]sulfonyl}phenyl)methyl]thieno[2,3-c]pyridine-2- carboxamideN-[(4-{[3-fluoro-5-(trifluoromethyl)benzene]sulfonyl}phenyl)methyl]-0.0112 0.00345 1H-pyrazolo[3,4-b]pyridine-5-carboxamideN-[(4-{[3-fluoro-5-(trifluoromethyl)benzene]sulfonyl}phenyl)methyl]-0.0262 0.0036 1H-pyrrolo[3,2-c]pyridine-2-carboxamideN-[(4-{[3-fluoro-5- 0.0074 0.0050(trifluoromethyl)benzene]sulfonyl}phenyl)methyl]furo[2,3-c]pyridine-2-carboxamide N-[(4-{[3-fluoro-5- 0.0059 0.0011(trifluoromethyl)benzene]sulfonyl}phenyl)methyl]imidazo[1,2-a]pyrimidine-6-carboxamide N-[(4-{[3-fluoro-5- 0.0102 0.0031(trifluoromethyl)benzene]sulfonyl}phenyl)methyl]thieno[2,3-c]pyridine-2-carboxamideN-[(4-{[4-(1-cyanocyclopentyl)benzene]sulfonyl}phenyl)methyl]-1H- 0.06010.0189 pyrrolo[3,2-c]pyridine-2-carboxamide N-[(4-{[4-(1- 0.0080 0.0060cyanocyclopentyl)benzene]sulfonyl}phenyl)methyl]furo[2,3-c]pyridine-2-carboxamide N-[(4-{[4-(1- 0.0107 0.0030cyanocyclopentyl)benzene]sulfonyl}phenyl)methyl]imidazo[1,2-a]pyridine-6-carboxamide N-[(4-{[4-(1- 0.0032 0.0047cyanocyclopentyl)benzene]sulfonyl}phenyl)methyl]imidazo[1,2-a]pyrimidine-6-carboxamide N-[(4-{[4-(1H-imidazol-1- <0.00065 0.0122yl)benzene]sulfonyl}phenyl)methyl]imidazo[1,2-a]pyrimidine-6-carboxamide N-[(4-{[4-(1H-imidazol-1- 0.0190 0.0137ylmethyl)benzene]sulfonyl}phenyl)methyl]furo[2,3-c]pyridine-2-carboxamide N-[(4-{[4-(1H-imidazol-1- 0.0053 0.0122ylmethyl)benzene]sulfonyl}phenyl)methyl]thieno[2,3-c]pyridine-2-carboxamideN-[(4-{[4-(1H-pyrazol-1-yl)benzene]sulfonyl}phenyl)methyl]-1H- 0.01230.0075 pyrazolo[3,4-b]pyridine-5-carboxamideN-[(4-{[4-(1H-pyrazol-1-yl)benzene]sulfonyl}phenyl)methyl]furo[2,3-0.0041 0.0073 c]pyridine-2-carboxamideN-[(4-{[4-(2-methylpropoxy)benzene]sulfonyl}phenyl)methyl]-1H- 0.02630.0162 pyrazolo[3,4-b]pyridine-5-carboxamideN-[(4-{[4-(2-methylpropoxy)benzene]sulfonyl}phenyl)methyl]-1H- 0.01270.0094 pyrrolo[3,2-c]pyridine-2-carboxamideN-[(4-{[4-(2-methylpropoxy)benzene]sulfonyl}phenyl)methyl]furo[2,3-0.0094 0.0116 c]pyridine-2-carboxamide N-[(4-{[4-(2- 0.0022 0.0027methylpropoxy)benzene]sulfonyl}phenyl)methyl]imidazo[1,2-a]pyridine-6-carboxamide N-[(4-{[4-(2- 0.0055 0.0052methylpropoxy)benzene]sulfonyl}phenyl)methyl]imidazo[1,2-a]pyrimidine-6-carboxamide N-[(4-{[4-(2- 0.0040 0.0103methylpropoxy)benzene]sulfonyl}phenyl)methyl]thieno[2,3-c]pyridine-2-carboxamideN-[(4-{[4-(4-ethoxyphenyl)benzene]sulfonyl}phenyl)methyl]-1H- 0.0090.0090 pyrrolo[3,2-c]pyridine-2-carboxamideN-[(4-{[4-(4-methylpiperazin-1-yl)benzene]sulfonyl}phenyl)methyl]-1H-0.004 0.0013 pyrazolo[3,4-b]pyridine-5-carboxamideN-[(4-{[4-(4-methylpiperazin-1-yl)benzene]sulfonyl}phenyl)methyl]-1H-0.003 0.0008 pyrrolo[3,2-c]pyridine-2-carboxamideN-[(4-{[4-(4-methylpiperazin-1- 0.001 0.0005yl)benzene]sulfonyl}phenyl)methyl]furo[2,3-c]pyridine-2-carboxamideN-[(4-{[4-(4-methylpiperazin-1- 0.001 0.0002yl)benzene]sulfonyl}phenyl)methyl]imidazo[1,2-a]pyridine-6- carboxamideN-[(4-{[4-(4-methylpiperazin-1- 0.001 0.0003yl)benzene]sulfonyl}phenyl)methyl]thieno[2,3-c]pyridine-2- carboxamideN-[(4-{[4-(difluoromethyl)-3- 0.0082 0.0279fluorobenzene]sulfonyl}phenyl)methyl]imidazo[1,2-a]pyrimidine-6-carboxamide N-[(4-{[4-(ethoxymethyl)benzene]sulfonyl}phenyl)methyl]-1H-0.0266 0.0128 pyrazolo[3,4-b]pyridine-5-carboxamideN-[(4-{[4-(ethoxymethyl)benzene]sulfonyl}phenyl)methyl]-1H- 0.02250.0068 pyrrolo[3,2-c]pyridine-2-carboxamideN-[(4-{[4-(ethoxymethyl)benzene]sulfonyl}phenyl)methyl]furo[2,3- 0.00490.0066 c]pyridine-2-carboxamideN-[(4-{[4-(ethoxymethyl)benzene]sulfonyl}phenyl)methyl]imidazo[1,2-0.0027 0.0052 a]pyrimidine-6-carboxamideN-[(4-{[4-(ethylcarbamoyl)benzene]sulfonyl}phenyl)methyl]-1H- 0.1030.0968 pyrazolo[3,4-b]pyridine-5-carboxamideN-[(4-{[4-(ethylcarbamoyl)benzene]sulfonyl}phenyl)methyl]-1H- 0.01450.0141 pyrrolo[3,2-c]pyridine-2-carboxamideN-[(4-{[4-(ethylcarbamoyl)benzene]sulfonyl}phenyl)methyl]furo[2,3-0.0045 0.0067 c]pyridine-2-carboxamide N-[(4-{[4- 0.0120 0.0063(ethylcarbamoyl)benzene]sulfonyl}phenyl)methyl]imidazo[1,2-a]pyridine-6-carboxamide N-[(4-{[4- 0.0226 0.0878(ethylcarbamoyl)benzene]sulfonyl}phenyl)methyl]imidazo[1,2-a]pyrimidine-6-carboxamideN-[(4-{[4-(ethylcarbamoyl)benzene]sulfonyl}phenyl)methyl]thieno[2,3-0.0015 0.0033 c]pyridine-2-carboxamideN-[(4-{[4-(hydroxymethyl)benzene]sulfonyl}phenyl)methyl]furo[2,3- 0.00490.0062 c]pyridine-2-carboxamide N-[(4-{[4- 0.0142 0.0129(hydroxymethyl)benzene]sulfonyl}phenyl)methyl]imidazo[1,2-a]pyridine-6-carboxamideN-[(4-{[4-(hydroxymethyl)benzene]sulfonyl}phenyl)methyl]thieno[2,3-0.0038 0.0066 c]pyridine-2-carboxamideN-[(4-{[4-(morpholin-4-yl)benzene]sulfonyl}phenyl)methyl]-1H- 0.004450.00247 pyrazolo[3,4-b]pyridine-5-carboxamideN-[(4-{[4-(morpholin-4-yl)benzene]sulfonyl}phenyl)methyl]furo[2,3-0.0046 0.0025 c]pyridine-2-carboxamide N-[(4-{[4-(morpholin-4- 0.00350.0009 yl)benzene]sulfonyl}phenyl)methyl]imidazo[1,2-a]pyridine-6-carboxamide N-[(4-{[4-(morpholin-4- 0.0017 0.0040yl)benzene]sulfonyl}phenyl)methyl]imidazo[1,2-a]pyrimidine-6-carboxamideN-[(4-{[4-(morpholin-4-yl)benzene]sulfonyl}phenyl)methyl]thieno[2,3-0.0016 0.0015 c]pyridine-2-carboxamideN-[(4-{[4-(propan-2-yl)benzene]sulfonyl}phenyl)methyl]furo[2,3- 0.01190.0080 c]pyridine-2-carboxamideN-[(4-{[4-(propan-2-yl)benzene]sulfonyl}phenyl)methyl]imidazo[1,2-0.0146 0.00666 a]pyridine-6-carboxamideN-[(4-{[4-(propan-2-yl)benzene]sulfonyl}phenyl)methyl]imidazo[1,2-0.0017 0.0081 a]pyrimidine-6-carboxamideN-[(4-{[4-(propan-2-yloxy)benzene]sulfonyl}phenyl)methyl]-1H- 0.00800.0066 pyrazolo[3,4-b]pyridine-5-carboxamideN-[(4-{[4-(propan-2-yloxy)benzene]sulfonyl}phenyl)methyl]furo[2,3-0.0068 0.0057 c]pyridine-2-carboxamide N-[(4-{[4-(propan-2- 0.00430.0032 yloxy)benzene]sulfonyl}phenyl)methyl]imidazo[1,2-a]pyrimidine-6-carboxamideN-[(4-{[4-(pyrrolidin-1-yl)benzene]sulfonyl}phenyl)methyl]-1H- 0.0060.0045 pyrazolo[3,4-b]pyridine-6-carboxamideN-[(4-{[4-(pyrrolidin-1-yl)benzene]sulfonyl}phenyl)methyl]imidazo[1,2-0.003 0.0014 a]pyridine-6-carboxamideN-[(4-{[4-(trifluoromethoxy)benzene]sulfonyl}phenyl)methyl]-1H- 0.03460.0223 pyrazolo[3,4-b]pyridine-5-carboxamideN-[(4-{[4-(trifluoromethoxy)benzene]sulfonyl}phenyl)methyl]furo[2,3-0.0094 0.0277 c]pyridine-2-carboxamide N-[(4-{[4- 0.0050 0.0176(trifluoromethoxy)benzene]sulfonyl}phenyl)methyl]imidazo[1,2-a]pyrimidine-6-carboxamideN-[(4-{[4-(trifluoromethyl)benzene]sulfonyl}phenyl)methyl]-1H- 0.01990.0194 pyrazolo[3,4-b]pyridine-5-carboxamideN-[(4-{[4-(trifluoromethyl)benzene]sulfonyl}phenyl)methyl]furo[2,3-0.0087 0.0198 c]pyridine-2-carboxamide N-[(4-{[4- 0.0060 0.0235(trifluoromethyl)benzene]sulfonyl}phenyl)methyl]imidazo[1,2-a]pyrimidine-6-carboxamideN-[(4-{[4-chloro-2-(trifluoromethyl)benzene]sulfonyl}phenyl)methyl]-0.147 0.0783 1H-pyrazolo[3,4-b]pyridine-5-carboxamideN-[(4-{[4-chloro-2-(trifluoromethyl)benzene]sulfonyl}phenyl)methyl]-0.0422 0.0174 1H-pyrrolo[3,2-c]pyridine-2-carboxamideN-[(4-{[4-chloro-2- 0.0098 0.0254(trifluoromethyl)benzene]sulfonyl}phenyl)methyl]furo[2,3-c]pyridine-2-carboxamide N-[(4-{[4-chloro-2- 0.0198 0.0085(trifluoromethyl)benzene]sulfonyl}phenyl)methyl]imidazo[1,2-a]pyridine-6-carboxamide N-[(4-{[4-chloro-2- 0.0079 0.0684(trifluoromethyl)benzene]sulfonyl}phenyl)methyl]imidazo[1,2-a]pyrimidine-6-carboxamide N-[(4-{[4-chloro-2- 0.0070 0.0096(trifluoromethyl)benzene]sulfonyl}phenyl)methyl]thieno[2,3-c]pyridine-2-carboxamide N-[(4-{[4-chloro-3- 0.0060 0.0069(trifluoromethyl)benzene]sulfonyl}phenyl)methyl]furo[2,3-c]pyridine-2-carboxamide N-[(4-{[4-chloro-3- 0.00984 0.00357(trifluoromethyl)benzene]sulfonyl}phenyl)methyl]imidazo[1,2-a]pyridine-6-carboxamide N-[(4-{[4-chloro-3- 0.0028 0.0043(trifluoromethyl)benzene]sulfonyl}phenyl)methyl]imidazo[1,2-a]pyrimidine-6-carboxamideN-[(4-{[4-fluoro-2-(propan-2-yloxy)benzene]sulfonyl}phenyl)methyl]-0.0254 0.0033 1H-pyrrolo[3,2-c]pyridine-2-carboxamideN-[(4-{[4-fluoro-2-(propan-2- 0.0156 0.0139yloxy)benzene]sulfonyl}phenyl)methyl]furo[2,3-c]pyridine-2- carboxamideN-[(4-{[4-fluoro-2-(propan-2- 0.0222 0.0021yloxy)benzene]sulfonyl}phenyl)methyl]imidazo[1,2-a]pyridine-6-carboxamide N-[(4-{[4-fluoro-2-(propan-2- 0.0035 0.0150yloxy)benzene]sulfonyl}phenyl)methyl]imidazo[1,2-a]pyrimidine-6-carboxamide N-[(4-{[4-fluoro-2-(propan-2- 0.0050 0.0016yloxy)benzene]sulfonyl}phenyl)methyl]thieno[2,3-c]pyridine-2-carboxamideN-[(4-{[4-fluoro-2-(trifluoromethyl)benzene]sulfonyl}phenyl)methyl]-0.112 0.109 1H-pyrazolo[3,4-b]pyridine-5-carboxamideN-[(4-{[4-fluoro-2-(trifluoromethyl)benzene]sulfonyl}phenyl)methyl]-0.0270 0.0141 1H-pyrrolo[3,2-c]pyridine-2-carboxamideN-[(4-{[4-fluoro-2- 0.0040 0.0150(trifluoromethyl)benzene]sulfonyl}phenyl)methyl]imidazo[1,2-a]pyridine-6-carboxamide N-[(4-{[4-fluoro-2- 0.0187 0.1-1(trifluoromethyl)benzene]sulfonyl}phenyl)methyl]imidazo[1,2-a]pyrimidine-6-carboxamide N-[(4-{[4-fluoro-2- 0.0064 0.0143(trifluoromethyl)benzene]sulfonyl}phenyl)methyl]thieno[2,3-c]pyridine-2-carboxamide N-[(4-{[4-fluoro-3-(2,2,2- 0.01 0.0147trifluoroethoxy)benzene]sulfonyl}phenyl)methyl]-1H-pyrazolo[3,4-b]pyridine-5-carboxamide N-[(4-{[4-fluoro-3-(2,2,2- 0.0103 0.0065trifluoroethoxy)benzene]sulfonyl}phenyl)methyl]-1H-pyrrolo[3,2-c]pyridine-2-carboxamide N-[(4-{[4-fluoro-3-(2,2,2- 0.0087 0.0255trifluoroethoxy)benzene]sulfonyl}phenyl)methyl]furo[2,3-c]pyridine-2-carboxamide N-[(4-{[4-fluoro-3-(2,2,2- 0.0024 0.0065trifluoroethoxy)benzene]sulfonyl}phenyl)methyl]imidazo[1,2-a]pyrimidine-6-carboxamide N-[(4-{[4-fluoro-3-(2,2,2- 0.0033 0.0118trifluoroethoxy)benzene]sulfonyl}phenyl)methyl]thieno[2,3-c]pyridine-2-carboxamideN-[(4-{[4-fluoro-3-(trifluoromethyl)benzene]sulfonyl}phenyl)methyl]-0.0394 0.0138 1H-pyrazolo[3,4-b]pyridine-5-carboxamideN-[(4-{[4-fluoro-3-(trifluoromethyl)benzene]sulfonyl}phenyl)methyl]-0.0164 0.0043 1H-pyrrolo[3,2-c]pyridine-2-carboxamideN-[(4-{[4-fluoro-3- 0.0082 0.0072(trifluoromethyl)benzene]sulfonyl}phenyl)methyl]furo[2,3-c]pyridine-2-carboxamide N-[(4-{[4-fluoro-3- 0.0040 0.0017(trifluoromethyl)benzene]sulfonyl}phenyl)methyl]imidazo[1,2-a]pyridine-6-carboxamide N-[(4-{[4-fluoro-3- 0.0080 0.0032(trifluoromethyl)benzene]sulfonyl}phenyl)methyl]imidazo[1,2-a]pyrimidine-6-carboxamide N-[(4-{[4-fluoro-3- 0.0040 0.0028(trifluoromethyl)benzene]sulfonyl}phenyl)methyl]thieno[2,3-c]pyridine-2-carboxamide N-[(4-{[4-methoxy-2- 0.0868 0.0628(trifluoromethyl)benzene]sulfonyl}phenyl)methyl]-1H-pyrazolo[3,4-b]pyridine-5-carboxamide N-[(4-{[4-methoxy-2- 0.0804 0.0130(trifluoromethyl)benzene]sulfonyl}phenyl)methyl]-1H-pyrrolo[3,2-c]pyridine-2-carboxamide N-[(4-{[4-methoxy-2- 0.0146 0.0152(trifluoromethyl)benzene]sulfonyl}phenyl)methyl]furo[2,3-c]pyridine-2-carboxamide N-[(4-{[4-methoxy-2- 0.0070 0.0657(trifluoromethyl)benzene]sulfonyl}phenyl)methyl]imidazo[1,2-a]pyrimidine-6-carboxamide N-[(4-{[4-methoxy-2- 0.0217 0.0130(trifluoromethyl)benzene]sulfonyl}phenyl)methyl]thieno[2,3-c]pyridine-2-carboxamideN-[(4-{[5-(diethylcarbamoyl)-2-fluorobenzene]sulfonyl}phenyl)methyl]-0.0384 0.0262 1H-pyrrolo[3,2-c]pyridine-2-carboxamideN-[(4-{[5-chloro-2-(2,2,2- 0.001 0.0003trifluoroethoxy)benzene]sulfonyl}phenyl)methyl]imidazo[1,2-a]pyridine-6-carboxamide N-[(4-{[5-chloro-2-(2,2- 0.005 0.0005difluoroethoxy)benzene]sulfonyl}phenyl)methyl]-1H-pyrrolo[3,2-c]pyridine-2-carboxamide N-[(4-{[5-chloro-2-(2,2- 0.002 0.0003difluoroethoxy)benzene]sulfonyl}phenyl)methyl]imidazo[1,2-a]pyridine-6-carboxamide N-[(4-{[5-chloro-2-(prop-2-yn-1- 0.007 0.0014yloxy)benzene]sulfonyl}phenyl)methyl]imidazo[1,2-a]pyridine-6-carboxamideN-[(4-{[5-chloro-2-(propan-2-yloxy)benzene]sulfonyl}phenyl)methyl]-0.0678 0.0271 1H-pyrazolo[3,4-b]pyridine-5-carboxamideN-[(4-{[5-chloro-2-(propan-2- 0.0091 0.0121yloxy)benzene]sulfonyl}phenyl)methyl]furo[2,3-c]pyridine-2- carboxamideN-[(4-{[5-chloro-2-(propan-2- 0.0047 0.0146yloxy)benzene]sulfonyl}phenyl)methyl]imidazo[1,2-a]pyrimidine-6-carboxamideN-[(4-{[5-fluoro-2-(hydroxymethyl)benzene]sulfonyl}phenyl)methyl]- 0.1090.1-1 1H-pyrazolo[3,4-b]pyridine-5-carboxamideN-[(4-{[5-fluoro-2-(hydroxymethyl)benzene]sulfonyl}phenyl)methyl]-0.0169 0.0675 1H-pyrrolo[3,2-c]pyridine-2-carboxamideN-[(4-{[5-fluoro-2- 0.0229 0.0670(hydroxymethyl)benzene]sulfonyl}phenyl)methyl]furo[2,3-c]pyridine-2-carboxamide N-[(4-{[5-fluoro-2- 0.0104 0.0650(hydroxymethyl)benzene]sulfonyl}phenyl)methyl]imidazo[1,2-a]pyridine-6-carboxamide N-[(4-{[5-fluoro-2- 0.0129 0.1-1(hydroxymethyl)benzene]sulfonyl}phenyl)methyl]imidazo[1,2-a]pyrimidine-6-carboxamide N-[(4-{[5-fluoro-2- 0.0077 0.0249(hydroxymethyl)benzene]sulfonyl}phenyl)methyl]thieno[2,3-c]pyridine-2-carboxamide N-[(4-{[5-hydroxy-2- 0.0219 0.0679(trifluoromethoxy)benzene]sulfonyl}phenyl)methyl]-1H-pyrazolo[3,4-b]pyridine-5-carboxamide N-[(4-{[5-hydroxy-2- 0.0064 0.0115(trifluoromethoxy)benzene]sulfonyl}phenyl)methyl]furo[2,3-c]pyridine-2-carboxamideN-[(4-{2-[ethyl(methyl)amino]-1,3-thiazole-5-sulfonyl}phenyl)methyl]-0.0036 0.0015 1H-pyrazolo[3,4-b]pyridine-5-carboxamideN-[(4-{2-[ethyl(methyl)amino]-1,3-thiazole-5- 0.0048 0.0009sulfonyl}phenyl)methyl]furo[2,3-c]pyridine-2-carboxamideN-[(4-{2-[ethyl(methyl)amino]-1,3-thiazole-5- 0.0033 0.0004sulfonyl}phenyl)methyl]imidazo[1,2-a]pyridine-6-carboxamideN-[(4-{2-[ethyl(methyl)amino]-1,3-thiazole-5- 0.0018 0.0009sulfonyl}phenyl)methyl]imidazo[1,2-a]pyrimidine-6-carboxamideN-[(4-{2-[ethyl(methyl)amino]-1,3-thiazole-5- 0.0029 0.0012sulfonyl}phenyl)methyl]thieno[2,3-c]pyridine-2-carboxamideN-[(4-{5H,6H,7H,8H,9H-imidazo[1,2-a]azepine-3- 0.0316 0.0123sulfonyl}phenyl)methyl]-1H-pyrazolo[3,4-b]pyridine-5-carboxamideN-[(4-{5H,6H,7H,8H,9H-imidazo[1,2-a]azepine-3- 0.0060 0.0057sulfonyl}phenyl)methyl]furo[2,3-c]pyridine-2-carboxamideN-[(4-{5H,6H,7H,8H,9H-imidazo[1,2-a]azepine-3- 0.0011 0.0287sulfonyl}phenyl)methyl]imidazo[1,2-a]pyrimidine-6-carboxamideN-[(4-{5H,6H,7H,8H,9H-imidazo[1,2-a]azepine-3- 0.0030 0.0008sulfonyl}phenyl)methyl]thieno[2,3-c]pyridine-2-carboxamideN-[(4-{6-chloroimidazo[1,2-a]pyridine-3-sulfonyl}phenyl)methyl]-1H-0.0033 0.0008 pyrazolo[3,4-b]pyridine-5-carboxamideN-[(4-{6-chloroimidazo[1,2-a]pyridine-3-sulfonyl}phenyl)methyl]-1H-0.0132 0.0014 pyrrolo[3,2-c]pyridine-2-carboxamideN-[(4-{6-chloroimidazo[1,2-a]pyridine-3- 0.0012 0.0004sulfonyl}phenyl)methyl]furo[2,3-c]pyridine-2-carboxamideN-[(4-{6-chloroimidazo[1,2-a]pyridine-3- 0.0053 0.0004sulfonyl}phenyl)methyl]imidazo[1,2-a]pyridine-6-carboxamideN-[(4-{6-chloroimidazo[1,2-a]pyridine-3- 0.0016 0.0004sulfonyl}phenyl)methyl]imidazo[1,2-a]pyrimidine-6-carboxamideN-[(4-{6-chloroimidazo[1,2-a]pyridine-3- 0.0012 0.0004sulfonyl}phenyl)methyl]thieno[2,3-c]pyridine-2-carboxamideN-[(4-{8-oxatricyclo[7.4.0.0²,⁷]trideca-1(13),2,4,6,9,11-hexaene-6-0.021 0.00752sulfonyl}phenyl)methyl]-1H-pyrazolo[3,4-b]pyridine-5-carboxamideN-[(4-{8-oxatricyclo[7.4.0.0²,⁷]trideca-1(13),2,4,6,9,11-hexaene-6-0.0124 0.0128 sulfonyl}phenyl)methyl]furo[2,3-c]pyridine-2-carboxamideN-[(4-{8-oxatricyclo[7.4.0.0²,⁷]trideca-1(13),2,4,6,9,11-hexaene-6-0.0017 0.0029sulfonyl}phenyl)methyl]imidazo[1,2-a]pyrimidine-6-carboxamideN-[(4-{8-thiatricyclo[7.4.0.0²,⁷]trideca-1(13),2,4,6,9,11-hexaene-6-0.0035 0.0032sulfonyl}phenyl)methyl]-1H-pyrrolo[3,2-c]pyridine-2-carboxamideN-[(4-{8-thiatricyclo[7.4.0.0²,⁷]trideca-1(13),2,4,6,9,11-hexaene-6-0.0087 0.012 sulfonyl}phenyl)methyl]furo[2,3-c]pyridine-2-carboxamideN-[(4-{8-thiatricyclo[7.4.0.0²,⁷]trideca-1(13),2,4,6,9,11-hexaene-6-0.0018 0.0020sulfonyl}phenyl)methyl]imidazo[1,2-a]pyrimidine-6-carboxamideN-[(4-{8-thiatricyclo[7.4.0.0²,⁷]trideca-1(13),2,4,6,9,11-hexaene-6-0.0014 0.0043 sulfonyl}phenyl)methyl]thieno[2,3-c]pyridine-2-carboxamideN-{[4-({3-[(2- 0.0193 0.0458methylpropyl)carbamoyl]benzene}sulfonyl)phenyl]methyl}-1H-pyrrolo[3,2-c]pyridine-2-carboxamide N-{[4-({3-[(2- 0.0169 0.0263methylpropyl)carbamoyl]benzene}sulfonyl)phenyl]methyl}furo[2,3-c]pyridine-2-carboxamide N-{[4-({3-[(2- 0.0070 0.0456methylpropyl)carbamoyl]benzene}sulfonyl)phenyl]methyl}imidazo[1,2-a]pyrimidine-6-carboxamide N-{[4-({3-[(2- 0.0052 0.0145methylpropyl)carbamoyl]benzene}sulfonyl)phenyl]methyl}thieno[2,3-c]pyridine-2-carboxamide N-{[4-({3- 0.0047 0.0062[(dimethylamino)methyl]benzene}sulfonyl)phenyl]methyl}furo[2,3-c]pyridine-2-carboxamide N-{[4-({3- 0.0044 0.0660[(dimethylamino)methyl]benzene}sulfonyl)phenyl]methyl}imidazo[1,2-a]pyrimidine-6-carboxamideN-{[4-({3-[(morpholin-4-yl)carbonyl]benzene}sulfonyl)phenyl]methyl}-0.1235 0.1-1 1H-pyrazolo[3,4-b]pyridine-5-carboxamideN-{[4-({3-[(propan-2- 0.0151 0.0157yl)carbamoyl]benzene}sulfonyl)phenyl]methyl}furo[2,3-c]pyridine-2-carboxamide N-{[4-({3-[(propan-2- 0.0222 0.0504yl)carbamoyl]benzene}sulfonyl)phenyl]methyl}imidazo[1,2-a]pyridine-6-carboxamide N-{[4-({3-[(propan-2- 0.0070 0.0658yl)carbamoyl]benzene}sulfonyl)phenyl]methyl}imidazo[1,2-a]pyrimidine-6-carboxamide N-{[4-({3-[(propan-2- 0.0027 0.0067yl)carbamoyl]benzene}sulfonyl)phenyl]methyl}thieno[2,3-c]pyridine-2-carboxamide N-{[4-({3-[2- 0.0118 0.0058(dimethylamino)ethoxy]benzene}sulfonyl)phenyl]methyl}furo[2,3-c]pyridine-2-carboxamideN-{[4-({3-[2-(dimethylamino)ethyl]benzene}sulfonyl)phenyl]methyl}-0.0292 0.0223 1H-pyrrolo[3,2-c]pyridine-2-carboxamide N-{[4-({3-[2-0.0035 0.1-1(dimethylamino)ethyl]benzene}sulfonyl)phenyl]methyl}imidazo[1,2-a]pyrimidine-6-carboxamide N-{[4-({3-[2- 0.0025 0.0016(dimethylamino)ethyl]benzene}sulfonyl)phenyl]methyl}thieno[2,3-c]pyridine-2-carboxamideN-{[4-({3-[2-(morpholin-4-yl)ethoxy]benzene}sulfonyl)phenyl]methyl}-0.0649 0.0126 1H-pyrrolo[3,2-c]pyridine-2-carboxamideN-{[4-({3-[2-(morpholin-4- 0.0068 0.0034yl)ethoxy]benzene}sulfonyl)phenyl]methyl}imidazo[1,2-a]pyridine-6-carboxamide N-{[4-({3-[2-(morpholin-4- 0.0031 0.0247yl)ethoxy]benzene}sulfonyl)phenyl]methyl}imidazo[1,2-a]pyrimidine-6-carboxamide N-{[4-({3-[2-(morpholin-4- 0.0030 0.0015yl)ethoxy]benzene}sulfonyl)phenyl]methyl}thieno[2,3-c]pyridine-2-carboxamide N-{[4-({4-[(1R)-1- 0.0285 0.0122hydroxybutyl]benzene}sulfonyl)phenyl]methyl}furo[2,3-c]pyridine-2-carboxamide N-{[4-({4-[(1R)-1- 0.0048 0.0142hydroxybutyl]benzene}sulfonyl)phenyl]methyl}imidazo[1,2-a]pyrimidine-6-carboxamide N-{[4-({4- 0.0033 0.0246[(dimethylamino)methyl]benzene}sulfonyl)phenyl]methyl}imidazo[1,2-a]pyrimidine-6-carboxamideN-{[4-({4-[(pyrrolidin-1-yl)carbonyl]benzene}sulfonyl)phenyl]methyl}-0.0158 0.0093 1H-pyrazolo[3,4-b]pyridine-5-carboxamideN-{[4-({4-[(pyrrolidin-1- 0.0015 0.0014yl)carbonyl]benzene}sulfonyl)phenyl]methyl}furo[2,3-c]pyridine-2-carboxamide N-{[4-({4-[(pyrrolidin-1- 0.0037 0.0017yl)carbonyl]benzene}sulfonyl)phenyl]methyl}thieno[2,3-c]pyridine-2-carboxamide N-{[4-({4-[2- 0.0021 0.0008(dimethylamino)ethyl]benzene}sulfonyl)phenyl]methyl}imidazo[1,2-a]pyridine-6-carboxamide N-{[4-({4-[2- 0.0020 0.0181(dimethylamino)ethyl]benzene}sulfonyl)phenyl]methyl}imidazo[1,2-a]pyrimidine-6-carboxamideN-{[4-({4-[2-(pyrrolidin-1-yl)ethoxy]benzene}sulfonyl)phenyl]methyl}-0.003 0.0023 1H-pyrrolo[3,2-c]pyridine-2-carboxamideN-{[4-({4-fluoro-3-[(propan-2- 0.0852 0.0631yl)carbamoyl]benzene}sulfonyl)phenyl]methyl}-1H-pyrazolo[3,4-b]pyridine-5-carboxamide N-{[4-({4-fluoro-3-[(propan-2- 0.0077 0.0854yl)carbamoyl]benzene}sulfonyl)phenyl]methyl}imidazo[1,2-a]pyrimidine-6-carboxamide N-{[4-({4-fluoro-3-[(propan-2- 0.0213 0.0068yl)carbamoyl]benzene}sulfonyl)phenyl]methyl}thieno[2,3-c]pyridine-2-carboxamideN-{[4-(1,3-thiazole-2-sulfonyl)phenyl]methyl}furo[2,3-c]pyridine-2-0.0198 0.0786 carboxamideN-{[4-(1,3-thiazole-2-sulfonyl)phenyl]methyl}imidazo[1,2-a]pyridine-6-0.021 0.0994 carboxamideN-{[4-(1,3-thiazole-2-sulfonyl)phenyl]methyl}thieno[2,3-c]pyridine-2-0.0144 0.0751 carboxamideN-{[4-(1,4-dimethyl-1H-imidazole-2-sulfonyl)phenyl]methyl}furo[2,3-0.0607 0.1-1 c]pyridine-2-carboxamideN-{[4-(1,4-dimethyl-1H-imidazole-2- 0.1-1 0.0954sulfonyl)phenyl]methyl}imidazo[1,2-a]pyridine-6-carboxamideN-{[4-(1,4-dimethyl-1H-imidazole-2- 0.0316   1-10sulfonyl)phenyl]methyl}imidazo[1,2-a]pyrimidine-6-carboxamideN-{[4-(1,5-dimethyl-1H-imidazole-2-sulfonyl)phenyl]methyl}furo[2,3-0.0574 0.0659 c]pyridine-2-carboxamideN-{[4-(1,5-dimethyl-1H-imidazole-2- 0.0309 0.0731sulfonyl)phenyl]methyl}imidazo[1,2-a]pyridine-6-carboxamideN-{[4-(1,5-dimethyl-1H-imidazole-2- 0.0329   1-10sulfonyl)phenyl]methyl}imidazo[1,2-a]pyrimidine-6-carboxamideN-{[4-(1-benzothiophene-7-sulfonyl)phenyl]methyl}-1H-pyrazolo[3,4-0.0099 0.0128 b]pyridine-5-carboxamideN-{[4-(1-benzothiophene-7-sulfonyl)phenyl]methyl}furo[2,3-c]pyridine-0.0049 0.0139 2-carboxamideN-{[4-(1-benzothiophene-7-sulfonyl)phenyl]methyl}thieno[2,3- 0.00150.0015 c]pyridine-2-carboxamideN-{[4-(1H-indole-7-sulfonyl)phenyl]methyl}-1H-pyrazolo[3,4- 0.01470.0432 b]pyridine-5-carboxamide N-{[4-(1-methyl-1H-1,3-benzodiazole-6-0.0040 0.0338sulfonyl)phenyl]methyl}imidazo[1,2-a]pyrimidine-6-carboxamideN-{[4-(1-methyl-1H-indazole-4-sulfonyl)phenyl]methyl}-1,3- 0.0098   1-10benzothiazole-6-carboxamideN-{[4-(1-methyl-1H-indazole-4-sulfonyl)phenyl]methyl}-1H- 0.0203 0.0064pyrazolo[3,4-b]pyridine-5-carboxamideN-{[4-(1-methyl-1H-indazole-4-sulfonyl)phenyl]methyl}-1H-pyrrolo[3,2-0.0031 0.0015 c]pyridine-2-carboxamideN-{[4-(1-methyl-1H-indazole-4-sulfonyl)phenyl]methyl}furo[2,3- 0.00920.0036 c]pyridine-2-carboxamideN-{[4-(1-methyl-1H-indazole-4-sulfonyl)phenyl]methyl}imidazo[1,2- 0.01250.0030 a]pyridine-6-carboxamideN-{[4-(1-methyl-1H-indazole-4-sulfonyl)phenyl]methyl}imidazo[1,2- 0.00420.0103 a]pyrimidine-6-carboxamideN-{[4-(1-methyl-1H-indazole-4-sulfonyl)phenyl]methyl}thieno[2,3- 0.00110.0008 c]pyridine-2-carboxamideN-{[4-(1-methyl-1H-indazole-5-sulfonyl)phenyl]methyl}-1H- 0.0054 0.00273pyrazolo[3,4-b]pyridine-5-carboxamideN-{[4-(1-methyl-1H-indazole-5-sulfonyl)phenyl]methyl}-1H-pyrrolo[3,2-0.0057 0.0031 c]pyridine-2-carboxamideN-{[4-(1-methyl-1H-indazole-5-sulfonyl)phenyl]methyl}furo[2,3- 0.00330.0035 c]pyridine-2-carboxamideN-{[4-(1-methyl-1H-indazole-5-sulfonyl)phenyl]methyl}imidazo[1,2- 0.00400.0016 a]pyridine-6-carboxamideN-{[4-(1-methyl-1H-indazole-5-sulfonyl)phenyl]methyl}imidazo[1,2- 0.00170.0049 a]pyrimidine-6-carboxamideN-{[4-(1-methyl-1H-indazole-5-sulfonyl)phenyl]methyl}thieno[2,3- 0.00150.0016 c]pyridine-2-carboxamideN-{[4-(1-methyl-1H-indazole-6-sulfonyl)phenyl]methyl}-1H- 0.004 0.0030pyrazolo[3,4-b]pyridine-5-carboxamideN-{[4-(1-methyl-1H-indazole-6-sulfonyl)phenyl]methyl}-1H-pyrrolo[3,2-0.0051 0.0033 c]pyridine-2-carboxamideN-{[4-(1-methyl-1H-indazole-6-sulfonyl)phenyl]methyl}furo[2,3- 0.00470.0034 c]pyridine-2-carboxamideN-{[4-(1-methyl-1H-indazole-6-sulfonyl)phenyl]methyl}imidazo[1,2- 0.00500.0039 a]pyridine-6-carboxamideN-{[4-(1-methyl-1H-indazole-6-sulfonyl)phenyl]methyl}imidazo[1,2- 0.00160.0050 a]pyrimidine-6-carboxamideN-{[4-(1-methyl-1H-indazole-6-sulfonyl)phenyl]methyl}thieno[2,3- 0.00230.0011 c]pyridine-2-carboxamideN-{[4-(1-methyl-1H-indazole-7-sulfonyl)phenyl]methyl}-1H- 0.0918 0.0869pyrazolo[3,4-b]pyridine-5-carboxamideN-{[4-(1-methyl-1H-indazole-7-sulfonyl)phenyl]methyl}-1H-pyrrolo[3,2-0.0371 0.0111 c]pyridine-2-carboxamideN-{[4-(1-methyl-1H-indazole-7-sulfonyl)phenyl]methyl}furo[2,3- 0.01150.0275 c]pyridine-2-carboxamideN-{[4-(1-methyl-1H-indazole-7-sulfonyl)phenyl]methyl}imidazo[1,2- 0.02870.0275 a]pyridine-6-carboxamideN-{[4-(1-methyl-1H-indazole-7-sulfonyl)phenyl]methyl}imidazo[1,2- 0.02330.1-1 a]pyrimidine-6-carboxamideN-{[4-(1-methyl-1H-indazole-7-sulfonyl)phenyl]methyl}thieno[2,3- 0.00450.0104 c]pyridine-2-carboxamideN-{[4-(1-methyl-1H-indole-2-sulfonyl)phenyl]methyl}-1H-pyrazolo[3,4-0.0140 0.0132 b]pyridine-5-carboxamideN-{[4-(1-methyl-1H-indole-2-sulfonyl)phenyl]methyl}thieno[2,3- 0.00520.0034 c]pyridine-2-carboxamideN-{[4-(1-methyl-1H-pyrazole-4-sulfonyl)phenyl]methyl}-1H- 0.182 0.1-1pyrazolo[3,4-b]pyridine-5-carboxamideN-{[4-(1-methyl-1H-pyrazole-4-sulfonyl)phenyl]methyl}furo[2,3- 0.01680.0654 c]pyridine-2-carboxamideN-{[4-(1-methyl-1H-pyrazole-4-sulfonyl)phenyl]methyl}imidazo[1,2- 0.00820.1-1 a]pyrimidine-6-carboxamideN-{[4-(1-propyl-1H-pyrazole-4-sulfonyl)phenyl]methyl}-1H- 0.008 0.0070pyrazolo[3,4-b]pyridine-5-carboxamideN-{[4-(1-propyl-1H-pyrazole-4-sulfonyl)phenyl]methyl}-1H-pyrrolo[3,2-0.0149 0.0059 c]pyridine-2-carboxamideN-{[4-(1-propyl-1H-pyrazole-4-sulfonyl)phenyl]methyl}furo[2,3- 0.00570.0064 c]pyridine-2-carboxamideN-{[4-(1-propyl-1H-pyrazole-4-sulfonyl)phenyl]methyl}imidazo[1,2- 0.00490.0052 a]pyridine-6-carboxamideN-{[4-(1-propyl-1H-pyrazole-4-sulfonyl)phenyl]methyl}thieno[2,3- 0.00190.0016 c]pyridine-2-carboxamide N-{[4-(2,3-dihydro-1,4-benzodioxine-6-0.0055 0.0062 sulfonyl)phenyl]methyl}furo[2,3-c]pyridine-2-carboxamideN-{[4-(2,3-dihydro-1,4-benzodioxine-6- 0.0002 0.0005sulfonyl)phenyl]methyl}imidazo[1,2-a]pyrimidine-6-carboxamideN-{[4-(2,3-dihydro-1-benzofuran-7-sulfonyl)phenyl]methyl}-1H- 0.02480.0147 pyrazolo[3,4-b]pyridine-5-carboxamideN-{[4-(2,3-dihydro-1-benzofuran-7-sulfonyl)phenyl]methyl}-1H- 0.01400.0038 pyrrolo[3,2-c]pyridine-2-carboxamideN-{[4-(2,3-dihydro-1-benzofuran-7-sulfonyl)phenyl]methyl}furo[2,3-0.0060 0.0071 c]pyridine-2-carboxamideN-{[4-(2,3-dihydro-1-benzofuran-7- 0.0125 0.0064sulfonyl)phenyl]methyl}imidazo[1,2-a]pyridine-6-carboxamideN-{[4-(2,3-dihydro-1-benzofuran-7- 0.0021 0.0258sulfonyl)phenyl]methyl}imidazo[1,2-a]pyrimidine-6-carboxamideN-{[4-(2,3-dihydro-1-benzofuran-7-sulfonyl)phenyl]methyl}thieno[2,3-0.0022 0.0030 c]pyridine-2-carboxamideN-{[4-(2,6-dimethoxypyridine-3-sulfonyl)phenyl]methyl}-1H- 0.0307 0.0020pyrazolo[3,4-b]pyridine-5-carboxamideN-{[4-(2,6-dimethoxypyridine-3-sulfonyl)phenyl]methyl}furo[2,3- 0.00660.011 c]pyridine-2-carboxamideN-{[4-(2,6-dimethoxypyridine-3-sulfonyl)phenyl]methyl}imidazo[1,2-0.0433 0.0092 a]pyridine-6-carboxamideN-{[4-(2H-1,3-benzodioxole-4-sulfonyl)phenyl]methyl}-1H- 0.047 0.0884pyrazolo[3,4-b]pyridine-5-carboxamideN-{[4-(2H-1,3-benzodioxole-4-sulfonyl)phenyl]methyl}-1H-pyrrolo[3,2-0.0205 0.0118 c]pyridine-2-carboxamideN-{[4-(2H-1,3-benzodioxole-4-sulfonyl)phenyl]methyl}furo[2,3- 0.02580.0266 c]pyridine-2-carboxamideN-{[4-(2H-1,3-benzodioxole-4-sulfonyl)phenyl]methyl}imidazo[1,2- 0.00710.0130 a]pyridine-6-carboxamideN-{[4-(2H-1,3-benzodioxole-4-sulfonyl)phenyl]methyl}imidazo[1,2- 0.00290.0933 a]pyrimidine-6-carboxamideN-{[4-(2H-1,3-benzodioxole-4-sulfonyl)phenyl]methyl}thieno[2,3- 0.00330.0072 c]pyridine-2-carboxamideN-{[4-(2H-1,3-benzodioxole-5-sulfonyl)phenyl]methyl}-1H- 0.0482 0.0074pyrazolo[3,4-b]pyridine-5-carboxamideN-{[4-(2H-1,3-benzodioxole-5-sulfonyl)phenyl]methyl}furo[2,3- 0.00530.0087 c]pyridine-2-carboxamideN-{[4-(2H-1,3-benzodioxole-5-sulfonyl)phenyl]methyl}imidazo[1,2- 0.01070.00533 a]pyridine-6-carboxamideN-{[4-(2H-1,3-benzodioxole-5-sulfonyl)phenyl]methyl}imidazo[1,2- 0.00300.0117 a]pyrimidine-6-carboxamideN-{[4-(2-methyl-1,3-thiazole-4-sulfonyl)phenyl]methyl}-1H- 0.0828 0.0207pyrazolo[3,4-b]pyridine-5-carboxamideN-{[4-(2-methyl-1,3-thiazole-4-sulfonyl)phenyl]methyl}furo[2,3- 0.03670.0690 c]pyridine-2-carboxamideN-{[4-(2-methyl-1,3-thiazole-4-sulfonyl)phenyl]methyl}imidazo[1,2-0.0286   1-10 a]pyrimidine-6-carboxamideN-{[4-(2-methyl-2H-indazole-5-sulfonyl)phenyl]methyl}imidazo[1,2- 0.01330.0058 a]pyridine-6-carboxamideN-{[4-(2-methyl-2H-indazole-5-sulfonyl)phenyl]methyl}imidazo[1,2- 0.00120.0082 a]pyrimidine-6-carboxamideN-{[4-(2-methyl-2H-indazole-5-sulfonyl)phenyl]methyl}thieno[2,3- 0.00550.0033 c]pyridine-2-carboxamideN-{[4-(2-methyl-2H-indazole-6-sulfonyl)phenyl]methyl}-1H- 0.0147 0.0070pyrazolo[3,4-b]pyridine-5-carboxamideN-{[4-(2-methyl-2H-indazole-6-sulfonyl)phenyl]methyl}-1H-pyrrolo[3,2-0.0025 0.0032 c]pyridine-2-carboxamideN-{[4-(2-methyl-2H-indazole-6-sulfonyl)phenyl]methyl}furo[2,3- 0.00340.0028 c]pyridine-2-carboxamideN-{[4-(2-methyl-2H-indazole-6-sulfonyl)phenyl]methyl}imidazo[1,2- 0.00190.0017 a]pyridine-6-carboxamideN-{[4-(2-methyl-2H-indazole-6-sulfonyl)phenyl]methyl}imidazo[1,2- 0.00120.0061 a]pyrimidine-6-carboxamideN-{[4-(2-methyl-2H-indazole-6-sulfonyl)phenyl]methyl}thieno[2,3- 0.00140.0015 c]pyridine-2-carboxamideN-{[4-(2-methylpyridine-3-sulfonyl)phenyl]methyl}-1H-pyrazolo[3,4-0.1045 0.1356 b]pyridine-5-carboxamideN-{[4-(2-methylpyridine-3-sulfonyl)phenyl]methyl}-1H-pyrrolo[3,2- 0.18030.0240 c]pyridine-2-carboxamideN-{[4-(2-methylpyridine-3-sulfonyl)phenyl]methyl}imidazo[1,2- 0.02080.1-1 a]pyrimidine-6-carboxamideN-{[4-(2-methylpyridine-3-sulfonyl)phenyl]methyl}thieno[2,3- 0.01540.0119 c]pyridine-2-carboxamideN-{[4-(4-methylpyridine-2-sulfonyl)phenyl]methyl}furo[2,3-c]pyridine-0.0192 0.0114 2-carboxamideN-{[4-(4-methylpyridine-3-sulfonyl)phenyl]methyl}-1H-pyrazolo[3,4- 0.1-10.2714 b]pyridine-5-carboxamideN-{[4-(4-methylpyridine-3-sulfonyl)phenyl]methyl}-1H-pyrrolo[3,2- 0.25990.0258 c]pyridine-2-carboxamideN-{[4-(4-methylpyridine-3-sulfonyl)phenyl]methyl}furo[2,3-c]pyridine-0.0252 0.062 2-carboxamideN-{[4-(4-methylpyridine-3-sulfonyl)phenyl]methyl}imidazo[1,2- 0.06650.0658 a]pyridine-6-carboxamideN-{[4-(4-methylpyridine-3-sulfonyl)phenyl]methyl}imidazo[1,2- 0.01910.1-1 a]pyrimidine-6-carboxamideN-{[4-(4-methylpyridine-3-sulfonyl)phenyl]methyl}thieno[2,3- 0.02920.0225 c]pyridine-2-carboxamideN-{[4-(4-methylthiophene-2-sulfonyl)phenyl]methyl}imidazo[1,2- 0.01240.0125 a]pyridine-6-carboxamideN-{[4-(5-chloro-3-methylpyridine-2-sulfonyl)phenyl]methyl}-1H- 0.06250.0753 pyrazolo[3,4-b]pyridine-5-carboxamideN-{[4-(5-chloro-3-methylpyridine-2-sulfonyl)phenyl]methyl}furo[2,3-0.0099 0.0165 c]pyridine-2-carboxamideN-{[4-(5-chloro-3-methylpyridine-2- 0.0188 0.0080sulfonyl)phenyl]methyl}imidazo[1,2-a]pyridine-6-carboxamideN-{[4-(5-chloro-3-methylpyridine-2- 0.0022 0.0220sulfonyl)phenyl]methyl}imidazo[1,2-a]pyrimidine-6-carboxamideN-{[4-(5-chloro-3-methylpyridine-2-sulfonyl)phenyl]methyl}thieno[2,3-0.0039 0.0072 c]pyridine-2-carboxamideN-{[4-(5-chloropyridine-3-sulfonyl)phenyl]methyl}-1H-pyrazolo[3,4-0.0238 0.0062 b]pyridine-5-carboxamideN-{[4-(5-chloropyridine-3-sulfonyl)phenyl]methyl}-1H-pyrrolo[3,2- 0.02000.0036 c]pyridine-2-carboxamideN-{[4-(5-chloropyridine-3-sulfonyl)phenyl]methyl}imidazo[1,2- 0.02440.0032 a]pyridine-6-carboxamideN-{[4-(5-fluoro-6-methylpyridine-2-sulfonyl)phenyl]methyl}furo[2,3-0.0062 0.0124 c]pyridine-2-carboxamideN-{[4-(5-fluoro-6-methylpyridine-2-sulfonyl)phenyl]methyl}thieno[2,3-0.0083 0.0071 c]pyridine-2-carboxamideN-{[4-(5-fluoropyridine-3-sulfonyl)phenyl]methyl}-1H-pyrazolo[3,4-0.0792 0.0254 b]pyridine-5-carboxamideN-{[4-(5-fluoropyridine-3-sulfonyl)phenyl]methyl}-1H-pyrrolo[3,2- 0.07130.0136 c]pyridine-2-carboxamideN-{[4-(5-fluoropyridine-3-sulfonyl)phenyl]methyl}imidazo[1,2- 0.02780.0137 a]pyridine-6-carboxamideN-{[4-(5-fluoropyridine-3-sulfonyl)phenyl]methyl}imidazo[1,2- 0.00670.0564 a]pyrimidine-6-carboxamideN-{[4-(5-fluoropyridine-3-sulfonyl)phenyl]methyl}thieno[2,3- 0.00970.0064 c]pyridine-2-carboxamideN-{[4-(5-methoxypyridine-2-sulfonyl)phenyl]methyl}furo[2,3- 0.00790.0316 c]pyridine-2-carboxamideN-{[4-(5-methoxypyridine-2-sulfonyl)phenyl]methyl}imidazo[1,2- 0.02290.0173 a]pyridine-6-carboxamideN-{[4-(5-methoxypyridine-2-sulfonyl)phenyl]methyl}thieno[2,3- 0.00710.0193 c]pyridine-2-carboxamideN-{[4-(5-methoxypyridine-3-sulfonyl)phenyl]methyl}-1H-pyrazolo[3,4-0.0414 0.0167 b]pyridine-5-carboxamideN-{[4-(5-methoxypyridine-3-sulfonyl)phenyl]methyl}imidazo[1,2- 0.00900.0034 a]pyridine-6-carboxamideN-{[4-(5-methoxypyridine-3-sulfonyl)phenyl]methyl}imidazo[1,2- 0.00160.0258 a]pyrimidine-6-carboxamideN-{[4-(5-methoxypyridine-3-sulfonyl)phenyl]methyl}thieno[2,3- 0.00900.0016 c]pyridine-2-carboxamideN-{[4-(5-methylpyridine-3-sulfonyl)phenyl]methyl}imidazo[1,2- 0.03680.0071 a]pyridine-6-carboxamideN-{[4-(5-methylpyridine-3-sulfonyl)phenyl]methyl}imidazo[1,2- 0.00220.0124 a]pyrimidine-6-carboxamideN-{[4-(5-methylpyridine-3-sulfonyl)phenyl]methyl}thieno[2,3- 0.00600.0025 c]pyridine-2-carboxamideN-{[4-(5-methylthiophene-2-sulfonyl)phenyl]methyl}-1H-pyrazolo[3,4-0.0223 0.0347 b]pyridine-5-carboxamideN-{[4-(6-methoxynaphthalene-2-sulfonyl)phenyl]methyl}-1H- 0.0099 0.0051pyrrolo[3,2-c]pyridine-2-carboxamideN-{[4-(6-methoxynaphthalene-2-sulfonyl)phenyl]methyl}furo[2,3- 0.00300.0036 c]pyridine-2-carboxamideN-{[4-(6-methoxynaphthalene-2-sulfonyl)phenyl]methyl}imidazo[1,2- 0.00270.0018 a]pyridine-6-carboxamideN-{[4-(6-methoxynaphthalene-2-sulfonyl)phenyl]methyl}thieno[2,3- 0.00150.0033 c]pyridine-2-carboxamideN-{[4-(6-methoxypyridine-2-sulfonyl)phenyl]methyl}furo[2,3- 0.00250.0032 c]pyridine-2-carboxamideN-{[4-(6-methoxypyridine-2-sulfonyl)phenyl]methyl}imidazo[1,2- 0.00520.0013 a]pyridine-6-carboxamideN-{[4-(6-methoxypyridine-2-sulfonyl)phenyl]methyl}imidazo[1,2- 0.00220.0059 a]pyrimidine-6-carboxamideN-{[4-(6-methylpyrazine-2-sulfonyl)phenyl]methyl}-1H-pyrazolo[3,4-0.0349 0.0312 b]pyridine-5-carboxamideN-{[4-(6-methylpyrazine-2-sulfonyl)phenyl]methyl}furo[2,3-c]pyridine-0.0209 0.0097 2-carboxamideN-{[4-(6-methylpyrazine-2-sulfonyl)phenyl]methyl}imidazo[1,2- 0.00100.0525 a]pyrimidine-6-carboxamideN-{[4-(6-methylpyrazine-2-sulfonyl)phenyl]methyl}thieno[2,3- 0.00480.0051 c]pyridine-2-carboxamideN-{[4-(6-methylpyridine-2-sulfonyl)phenyl]methyl}furo[2,3-c]pyridine-0.0128 0.0125 2-carboxamideN-{[4-(6-methylpyridine-3-sulfonyl)phenyl]methyl}-1H-pyrazolo[3,4-0.0241 0.0213 b]pyridine-5-carboxamideN-{[4-(6-methylpyridine-3-sulfonyl)phenyl]methyl}-1H-pyrrolo[3,2- 0.05570.0130 c]pyridine-2-carboxamideN-{[4-(6-methylpyridine-3-sulfonyl)phenyl]methyl}imidazo[1,2- 0.02150.0139 a]pyridine-6-carboxamideN-{[4-(6-methylpyridine-3-sulfonyl)phenyl]methyl}imidazo[1,2- 0.00590.0555 a]pyrimidine-6-carboxamideN-{[4-(6-methylpyridine-3-sulfonyl)phenyl]methyl}thieno[2,3- 0.02200.0063 c]pyridine-2-carboxamideN-{[4-(benzenesulfonyl)phenyl]methyl}-[1,3]thiazolo[5,4-c]pyridine-2-0.220 >10 carboxamideN-{[4-(benzenesulfonyl)phenyl]methyl}-1,6-naphthyridine-2- 2.85 >10carboxamideN-{[4-(benzenesulfonyl)phenyl]methyl}-1H-pyrrolo[3,2-c]pyridine-3- 1.912.06 carboxamideN-{[4-(benzenesulfonyl)phenyl]methyl}furo[2,3-c]pyridine-2- 0.007 0.0088carboxamideN-{[4-(benzenesulfonyl)phenyl]methyl}imidazo[1,2-a]pyrimidine-6- 0.0020.057 carboxamideN-{[4-(benzenesulfonyl)phenyl]methyl}quinoline-6-carboxamide 0.108 >10N-{[4-(cyclohexanesulfonyl)phenyl]methyl}-1H-pyrrolo[3,2-c]pyridine-0.005 0.0176 2-carboxamideN-{[4-(dimethyl-1,3-thiazole-5-sulfonyl)phenyl]methyl}-1H- 0.0386 0.0164pyrazolo[3,4-b]pyridine-5-carboxamideN-{[4-(dimethyl-1,3-thiazole-5-sulfonyl)phenyl]methyl}furo[2,3- 0.00830.0103 c]pyridine-2-carboxamideN-{[4-(dimethyl-1,3-thiazole-5-sulfonyl)phenyl]methyl}imidazo[1,2- 0.0090.0037 a]pyridine-6-carboxamideN-{[4-(dimethyl-1,3-thiazole-5-sulfonyl)phenyl]methyl}imidazo[1,2-0.0037 0.0495 a]pyrimidine-6-carboxamideN-{[4-(dimethyl-1,3-thiazole-5-sulfonyl)phenyl]methyl}thieno[2,3- 0.00130.0030 c]pyridine-2-carboxamideN-{[4-(furan-2-sulfonyl)phenyl]methyl}imidazo[1,2-a]pyridine-6- 0.07620.1-1 carboxamideN-{[4-(isoquinoline-4-sulfonyl)phenyl]methyl}-1H-pyrazolo[3,4- 0.00370.0025 b]pyridine-5-carboxamideN-{[4-(isoquinoline-4-sulfonyl)phenyl]methyl}-1H-pyrrolo[3,2- 0.01090.0016 c]pyridine-2-carboxamideN-{[4-(isoquinoline-4-sulfonyl)phenyl]methyl}furo[2,3-c]pyridine-2-0.0190 0.003 carboxamideN-{[4-(isoquinoline-4-sulfonyl)phenyl]methyl}imidazo[1,2-a]pyridine-6-0.0224 0.0041 carboxamideN-{[4-(isoquinoline-4-sulfonyl)phenyl]methyl}imidazo[1,2- 0.0016 0.0032a]pyrimidine-6-carboxamideN-{[4-(isoquinoline-4-sulfonyl)phenyl]methyl}thieno[2,3-c]pyridine-2-0.0067 0.0008 carboxamideN-{[4-(naphthalene-1-sulfonyl)phenyl]methyl}-1H-pyrazolo[3,4- 0.00910.00368 b]pyridine-5-carboxamideN-{[4-(naphthalene-1-sulfonyl)phenyl]methyl}furo[2,3-c]pyridine-2-0.0049 0.0031 carboxamideN-{[4-(naphthalene-1-sulfonyl)phenyl]methyl}imidazo[1,2- 0.0029 0.0036a]pyrimidine-6-carboxamideN-{[4-(phenoxathiine-4-sulfonyl)phenyl]methyl}-1H-pyrazolo[3,4- 0.01480.0204 b]pyridine-5-carboxamideN-{[4-(phenoxathiine-4-sulfonyl)phenyl]methyl}furo[2,3-c]pyridine-2-0.0056 0.0131 carboxamideN-{[4-(phenoxathiine-4-sulfonyl)phenyl]methyl}imidazo[1,2-a]pyridine-0.00215 0.00218 6-carboxamideN-{[4-(phenoxathiine-4-sulfonyl)phenyl]methyl}imidazo[1,2- 0.0021 0.0042a]pyrimidine-6-carboxamideN-{[4-(pyridine-2-sulfonyl)phenyl]methyl}furo[2,3-c]pyridine-2- 0.05510.0870 carboxamideN-{[4-(pyridine-3-sulfonyl)phenyl]methyl}furo[2,3-c]pyridine-2- 0.00900.0664 carboxamideN-{[4-(pyridine-3-sulfonyl)phenyl]methyl}imidazo[1,2-a]pyrimidine-6-0.0059 0.1-1 carboxamideN-{[4-(quinoline-3-sulfonyl)phenyl]methyl}-1H-pyrazolo[3,4-b]pyridine-0.0052 0.0044 5-carboxamideN-{[4-(quinoline-3-sulfonyl)phenyl]methyl}-1H-pyrrolo[3,2-c]pyridine-0.0163 0.0029 2-carboxamideN-{[4-(quinoline-3-sulfonyl)phenyl]methyl}furo[2,3-c]pyridine-2- 0.00420.0032 carboxamideN-{[4-(quinoline-3-sulfonyl)phenyl]methyl}imidazo[1,2-a]pyridine-6-0.014 0.001 carboxamideN-{[4-(quinoline-3-sulfonyl)phenyl]methyl}imidazo[1,2-a]pyrimidine-6-0.0025 0.0036 carboxamideN-{[4-(quinoline-3-sulfonyl)phenyl]methyl}thieno[2,3-c]pyridine-2-0.0044 0.0009 carboxamideN-{[4-(quinoline-6-sulfonyl)phenyl]methyl}-1H-pyrazolo[3,4-b]pyridine-0.0101 0.0041 5-carboxamideN-{[4-(quinoline-6-sulfonyl)phenyl]methyl}furo[2,3-c]pyridine-2- 0.00730.005 carboxamideN-{[4-(quinoline-6-sulfonyl)phenyl]methyl}imidazo[1,2-a]pyridine-6-0.00516 0.00083 carboxamideN-{[4-(quinoline-6-sulfonyl)phenyl]methyl}imidazo[1,2-a]pyrimidine-6-0.0033 0.0056 carboxamideN-{[4-(quinoline-8-sulfonyl)phenyl]methyl}-1H-pyrazolo[3,4-b]pyridine-0.0455 0.0236 5-carboxamideN-{[4-(quinoline-8-sulfonyl)phenyl]methyl}furo[2,3-c]pyridine-2- 0.00760.0060 carboxamideN-{[4-(quinoline-8-sulfonyl)phenyl]methyl}imidazo[1,2-a]pyridine-6-0.0098 0.0055 carboxamideN-{[4-(quinoline-8-sulfonyl)phenyl]methyl}imidazo[1,2-a]pyrimidine-6-0.0030 0.0277 carboxamideN-({4-[(2,4-dimethoxyphenyl)sulfamoyl]phenyl}methyl)-1H- 0.0058 0.0069pyrrolo[3,2-c]pyridine-2-carboxamideN-[(4-{[2-(2-hydroxyethyl)phenyl]sulfamoyl}phenyl)methyl]-1H- 0.01880.0199 pyrrolo[3,2-c]pyridine-2-carboxamideN-({4-[(5-fluoro-2-methoxyphenyl)sulfamoyl]phenyl}methyl)quinoline-0.0660   1-10 6-carboxamideN-({4-[(2,3,6-trimethoxybenzene)sulfonyl]phenyl}methyl)thieno[2,3- 0.0120.0055 c]pyridine-2-carboxamideN-({4-[(2,3-dimethoxy-5-methylbenzene)sulfonyl]phenyl}methyl)-1H- 0.0100.002 pyrrolo[3,2-c]pyridine-2-carboxamide N-({4-[(2,3-dimethoxy-5-0.006 0.0027methylbenzene)sulfonyl]phenyl}methyl)thieno[2,3-c]pyridine-2-carboxamideN-({4-[(2,3-dimethoxybenzene)sulfonyl]phenyl}methyl)thieno[2,3- 0.0090.0034 c]pyridine-2-carboxamideN-({4-[(2,3-dimethylbenzene)sulfonyl]phenyl}methyl)-1H-pyrrolo[3,2-0.014 0.007 c]pyridine-2-carboxamideN-({4-[(2,3-dimethylbenzene)sulfonyl]phenyl}methyl)thieno[2,3- 0.0110.0044 c]pyridine-2-carboxamideN-({4-[(2,4,5-trimethylbenzene)sulfonyl]phenyl}methyl)thieno[2,3- 0.0080.0081 c]pyridine-2-carboxamideN-({4-[(2,4,6-trimethylbenzene)sulfonyl]phenyl}methyl)-1H- 0.076 0.046pyrrolo[3,2-c]pyridine-2-carboxamideN-({4-[(2,4-dimethoxybenzene)sulfonyl]phenyl}methyl)-1H-pyrrolo[3,2-0.027 0.007 c]pyridine-2-carboxamideN-({4-[(2,4-dimethylbenzene)sulfonyl]phenyl}methyl)-1H-pyrrolo[3,2-0.021 0.012 c]pyridine-2-carboxamideN-({4-[(2,4-dimethylbenzene)sulfonyl]phenyl}methyl)thieno[2,3- 0.0120.0222 c]pyridine-2-carboxamideN-({4-[(2,5-dimethoxybenzene)sulfonyl]phenyl}methyl)-1H-pyrrolo[3,2-0.017 0.006 c]pyridine-2-carboxamideN-({4-[(2,5-dimethoxybenzene)sulfonyl]phenyl}methyl)thieno[2,3- 0.0040.0023 c]pyridine-2-carboxamideN-({4-[(2,5-dimethylbenzene)sulfonyl]phenyl}methyl)-1H-pyrrolo[3,2-0.011 0.014 c]pyridine-2-carboxamideN-({4-[(2,5-dimethylbenzene)sulfonyl]phenyl}methyl)thieno[2,3- 0.0110.0086 c]pyridine-2-carboxamideN-({4-[(2,6-dimethoxy-4-methylbenzene)sulfonyl]phenyl}methyl)-1H- 0.0160.010 pyrrolo[3,2-c]pyridine-2-carboxamide N-({4-[(2,6-dimethoxy-4-0.007 0.0030methylbenzene)sulfonyl]phenyl}methyl)thieno[2,3-c]pyridine-2-carboxamideN-({4-[(2-acetylbenzene)sulfonyl]phenyl}methyl)-1H-pyrrolo[3,2- 0.0060.004 c]pyridine-2-carboxamideN-({4-[(2-acetylbenzene)sulfonyl]phenyl}methyl)thieno[2,3-c]pyridine-0.001 0.0010 2-carboxamideN-({4-[(2-chloro-6-methoxybenzene)sulfonyl]phenyl}methyl)-1H- 0.0130.003 pyrrolo[3,2-c]pyridine-2-carboxamideN-({4-[(2-chlorobenzene)sulfonyl]phenyl}methyl)-1H-pyrrolo[3,2- 0.0060.117 c]pyridine-2-carboxamideN-({4-[(2-ethoxybenzene)sulfonyl]phenyl}methyl)-1H-pyrrolo[3,2- 0.0110.002 c]pyridine-2-carboxamideN-({4-[(2-ethoxybenzene)sulfonyl]phenyl}methyl)thieno[2,3- 0.002 0.0008c]pyridine-2-carboxamideN-({4-[(2-ethylbenzene)sulfonyl]phenyl}methyl)-1H-pyrrolo[3,2- 0.0050.003 c]pyridine-2-carboxamideN-({4-[(2-ethylbenzene)sulfonyl]phenyl}methyl)thieno[2,3-c]pyridine-0.005 0.0029 2-carboxamideN-({4-[(2-fluoro-3-methoxybenzene)sulfonyl]phenyl}methyl)-1H- 0.0100.007 pyrrolo[3,2-c]pyridine-2-carboxamideN-({4-[(2-fluoro-4-methylbenzene)sulfonyl]phenyl}methyl)-1H- 0.011 0.021pyrrolo[3,2-c]pyridine-2-carboxamideN-({4-[(2-fluoro-4-methylbenzene)sulfonyl]phenyl}methyl)thieno[2,3-0.008 0.0207 c]pyridine-2-carboxamideN-({4-[(2-fluoro-5-methylbenzene)sulfonyl]phenyl}methyl)-1H- 0.025 0.024pyrrolo[3,2-c]pyridine-2-carboxamideN-({4-[(2-methanesulfonamidobenzene)sulfonyl]phenyl}methyl)-1H- 0.284 >1pyrrolo[3,2-c]pyridine-2-carboxamideN-({4-[(2-methoxy-5-methylbenzene)sulfonyl]phenyl}methyl)-1H- 0.0120.003 pyrrolo[3,2-c]pyridine-2-carboxamide N-({4-[(2-methoxy-5- 0.0060.0025 methylbenzene)sulfonyl]phenyl}methyl)thieno[2,3-c]pyridine-2-carboxamideN-({4-[(2-methoxybenzene)sulfonyl]phenyl}methyl)-1H-pyrrolo[3,2- 0.0090.007 c]pyridine-2-carboxamideN-({4-[(2-methoxybenzene)sulfonyl]phenyl}methyl)thieno[2,3- 0.007 0.0053c]pyridine-2-carboxamideN-({4-[(2-methylbenzene)sulfonyl]phenyl}methyl)-1H-pyrrolo[3,2- 0.0140.013 c]pyridine-2-carboxamideN-({4-[(2-methylbenzene)sulfonyl]phenyl}methyl)thieno[2,3- 0.010 0.0222c]pyridine-2-carboxamideN-({4-[(2-phenoxybenzene)sulfonyl]phenyl}methyl)-1H-pyrrolo[3,2- 0.0110.007 c]pyridine-2-carboxamideN-({4-[(2-phenoxybenzene)sulfonyl]phenyl}methyl)thieno[2,3- 0.011 0.0697c]pyridine-2-carboxamideN-({4-[(2-phenylethane)sulfonyl]phenyl}methyl)-1H-pyrrolo[3,2- 0.0110.022 c]pyridine-2-carboxamideN-({4-[(3,4-difluorobenzene)sulfonyl]phenyl}methyl)-1H-pyrrolo[3,2-0.013 0.014 c]pyridine-2-carboxamideN-({4-[(3,4-difluorobenzene)sulfonyl]phenyl}methyl)thieno[2,3- 0.0090.0081 c]pyridine-2-carboxamideN-({4-[(3,4-dimethoxybenzene)sulfonyl]phenyl}methyl)-1H-pyrrolo[3,2-0.014 0.003 c]pyridine-2-carboxamideN-({4-[(3,4-dimethoxybenzene)sulfonyl]phenyl}methyl)thieno[2,3- 0.0030.0009 c]pyridine-2-carboxamideN-({4-[(3,4-dimethylbenzene)sulfonyl]phenyl}methyl)thieno[2,3- 0.0060.0023 c]pyridine-2-carboxamideN-({4-[(3,5-dichlorobenzene)sulfonyl]phenyl}methyl)thieno[2,3- 0.0060.0007 c]pyridine-2-carboxamideN-({4-[(3,5-difluorobenzene)sulfonyl]phenyl}methyl)-1H-pyrrolo[3,2-0.011 0.007 c]pyridine-2-carboxamideN-({4-[(3,5-difluorobenzene)sulfonyl]phenyl}methyl)thieno[2,3- 0.0040.0027 c]pyridine-2-carboxamideN-({4-[(3,5-dimethylbenzene)sulfonyl]phenyl}methyl)-1H-pyrrolo[3,2-0.009 0.002 c]pyridine-2-carboxamideN-({4-[(3,5-dimethylbenzene)sulfonyl]phenyl}methyl)thieno[2,3- 0.0050.0018 c]pyridine-2-carboxamideN-({4-[(3-acetylbenzene)sulfonyl]phenyl}methyl)-1H-pyrrolo[3,2- 0.0120.006 c]pyridine-2-carboxamideN-({4-[(3-acetylbenzene)sulfonyl]phenyl}methyl)thieno[2,3-c]pyridine-0.004 0.0026 2-carboxamideN-({4-[(3-chlorobenzene)sulfonyl]phenyl}methyl)-1H-pyrrolo[3,2- 0.0050.003 c]pyridine-2-carboxamideN-({4-[(3-chlorobenzene)sulfonyl]phenyl}methyl)thieno[2,3-c]pyridine-0.005 0.003 2-carboxamideN-({4-[(3-ethylbenzene)sulfonyl]phenyl}methyl)thieno[2,3-c]pyridine-0.006 0.0027 2-carboxamideN-({4-[(3-fluoro-4-methoxybenzene)sulfonyl]phenyl}methyl)-1H- 0.0050.004 pyrrolo[3,2-c]pyridine-2-carboxamideN-({4-[(3-fluoro-4-methoxybenzene)sulfonyl]phenyl}methyl)thieno[2,3-0.005 0.0025 c]pyridine-2-carboxamideN-({4-[(3-fluoro-4-methylbenzene)sulfonyl]phenyl}methyl)-1H- 0.008 0.006pyrrolo[3,2-c]pyridine-2-carboxamideN-({4-[(3-fluoro-4-methylbenzene)sulfonyl]phenyl}methyl)thieno[2,3-0.003 0.0028 c]pyridine-2-carboxamideN-({4-[(3-fluorobenzene)sulfonyl]phenyl}methyl)-1H-pyrrolo[3,2- 0.0090.01 c]pyridine-2-carboxamideN-({4-[(3-fluorobenzene)sulfonyl]phenyl}methyl)thieno[2,3-c]pyridine-0.003 0.0033 2-carboxamideN-({4-[(3-methoxybenzene)sulfonyl]phenyl}methyl)-1H-pyrrolo[3,2- 0.0070.004 c]pyridine-2-carboxamideN-({4-[(3-methoxybenzene)sulfonyl]phenyl}methyl)thieno[2,3- 0.005 0.0026c]pyridine-2-carboxamideN-({4-[(3-methylbenzene)sulfonyl]phenyl}methyl)-1H-pyrrolo[3,2- 0.0090.004 c]pyridine-2-carboxamideN-({4-[(3-methylbenzene)sulfonyl]phenyl}methyl)thieno[2,3- 0.004 0.0023c]pyridine-2-carboxamideN-({4-[(4,5-difluoro-2-methoxybenzene)sulfonyl]phenyl}methyl)-1H- 0.0140.006 pyrrolo[3,2-c]pyridine-2-carboxamide N-({4-[(4,5-difluoro-2- 0.0050.0029 methoxybenzene)sulfonyl]phenyl}methyl)thieno[2,3-c]pyridine-2-carboxamideN-({4-[(4-acetylbenzene)sulfonyl]phenyl}methyl)-1H-pyrrolo[3,2- 0.0070.003 c]pyridine-2-carboxamideN-({4-[(4-acetylbenzene)sulfonyl]phenyl}methyl)thieno[2,3-c]pyridine-0.004 0.0025 2-carboxamideN-({4-[(4-chloro-2-methoxybenzene)sulfonyl]phenyl}methyl)-1H- 0.0220.003 pyrrolo[3,2-c]pyridine-2-carboxamide N-({4-[(4-chloro-2- 0.0100.0038 methoxybenzene)sulfonyl]phenyl}methyl)thieno[2,3-c]pyridine-2-carboxamide N-({4-[(4-chloro-2-methylbenzene)sulfonyl]phenyl}methyl)-1H-0.027 0.025 pyrrolo[3,2-c]pyridine-2-carboxamideN-({4-[(4-chloro-3-fluorobenzene)sulfonyl]phenyl}methyl)-1H- 0.008 0.013pyrrolo[3,2-c]pyridine-2-carboxamideN-({4-[(4-chloro-3-fluorobenzene)sulfonyl]phenyl}methyl)thieno[2,3-0.003 0.0071 c]pyridine-2-carboxamideN-({4-[(4-chlorobenzene)sulfonyl]phenyl}methyl)-1H-pyrrolo[3,2- 0.0090.025 c]pyridine-2-carboxamideN-({4-[(4-ethylbenzene)sulfonyl]phenyl}methyl)-1H-pyrrolo[3,2- 0.0080.012 c]pyridine-2-carboxamideN-({4-[(4-ethylbenzene)sulfonyl]phenyl}methyl)thieno[2,3-c]pyridine-0.006 0.0078 2-carboxamideN-({4-[(4-fluoro-2-methoxybenzene)sulfonyl]phenyl}methyl)-1H- 0.0310.007 pyrrolo[3,2-c]pyridine-2-carboxamideN-({4-[(4-fluoro-2-methoxybenzene)sulfonyl]phenyl}methyl)thieno[2,3-0.009 0.0065 c]pyridine-2-carboxamideN-({4-[(4-fluoro-2-methylbenzene)sulfonyl]phenyl}methyl)-1H- 0.019 0.027pyrrolo[3,2-c]pyridine-2-carboxamideN-({4-[(4-fluoro-3-methylbenzene)sulfonyl]phenyl}methyl)-1H- 0.009 0.007pyrrolo[3,2-c]pyridine-2-carboxamideN-({4-[(4-fluoro-3-methylbenzene)sulfonyl]phenyl}methyl)thieno[2,3-0.007 0.0029 c]pyridine-2-carboxamideN-({4-[(4-fluorobenzene)sulfonyl]phenyl}methyl)-1H-pyrrolo[3,2- 0.0380.008 c]pyridine-2-carboxamideN-({4-[(4-fluorobenzene)sulfonyl]phenyl}methyl)imidazo[1,2- 0.023 0.011a]pyridine-6-carboxamideN-({4-[(4-fluorobenzene)sulfonyl]phenyl}methyl)thieno[2,3-c]pyridine-0.003 0.010 2-carboxamideN-({4-[(4-methanesulfonylbenzene)sulfonyl]phenyl}methyl)-1H- 0.024 0.012pyrrolo[3,2-c]pyridine-2-carboxamideN-({4-[(4-methoxy-2-methylbenzene)sulfonyl]phenyl}methyl)-1H- 0.0240.024 pyrrolo[3,2-c]pyridine-2-carboxamideN-({4-[(4-methoxy-3-methylbenzene)sulfonyl]phenyl}methyl)-1H- 0.01 0.002pyrrolo[3,2-c]pyridine-2-carboxamide N-({4-[(4-methoxy-3- 0.003 0.0024methylbenzene)sulfonyl]phenyl}methyl)thieno[2,3-c]pyridine-2-carboxamideN-({4-[(4-methoxybenzene)sulfonyl]phenyl}methyl)-1H-pyrrolo[3,2- 0.0110.009 c]pyridine-2-carboxamideN-({4-[(4-methoxybenzene)sulfonyl]phenyl}methyl)thieno[2,3- 0.005 0.0027c]pyridine-2-carboxamideN-({4-[(4-methylbenzene)sulfonyl]phenyl}methyl)-1H-pyrrolo[3,2- 0.0060.009 c]pyridine-2-carboxamideN-({4-[(4-methylbenzene)sulfonyl]phenyl}methyl)thieno[2,3- 0.005 0.0050c]pyridine-2-carboxamideN-({4-[(5-acetyl-2-methoxybenzene)sulfonyl]phenyl}methyl)-1H- 0.02 0.006pyrrolo[3,2-c]pyridine-2-carboxamideN-({4-[(5-chloro-2-methoxybenzene)sulfonyl]phenyl}methyl)-1H- 0.0060.002 pyrrolo[3,2-c]pyridine-2-carboxamide N-({4-[(5-chloro-2- 0.0040.0013 methoxybenzene)sulfonyl]phenyl}methyl)thieno[2,3-c]pyridine-2-carboxamideN-({4-[(5-fluoro-2-methoxybenzene)sulfonyl]phenyl}methyl)-1H- 0.0050.003 pyrrolo[3,2-c]pyridine-2-carboxamideN-({4-[(5-fluoro-2-methylbenzene)sulfonyl]phenyl}methyl)-1H- 0.011 0.007pyrrolo[3,2-c]pyridine-2-carboxamideN-({4-[(5-fluoro-2-methylbenzene)sulfonyl]phenyl}methyl)thieno[2,3-0.003 0.0094 c]pyridine-2-carboxamideN-({4-[(5-tert-butyl-2-methoxybenzene)sulfonyl]phenyl}methyl)-1H- 0.6470.006 pyrrolo[3,2-c]pyridine-2-carboxamide N-({4-[(5-tert-butyl- 0.0150.0046 2-methoxybenzene)sulfonyl]phenyl}methyl)thieno[2,3-c]pyridine-2-carboxamide N-(4-(2-(trifluoromethoxy)phenylsulfonyl)benzyl)imidazo[1,2-0.008 a]pyridine-6-carboxamideN-(4-(phenylsulfonyl)benzyl)-1H-imidazo[4,5-b]pyridine-6-carboxamide5.780 >10 N-(4-(phenylsulfonyl)benzyl)benzo[d]thiazole-5-carboxamide0.047 3.872N-[(4-{[2-(benzyloxy)benzene]sulfonyl}phenyl)methyl]-1H-pyrrolo[3,2-0.018 0.033 c]pyridine-2-carboxamideN-[(4-{[2-(dimethylcarbamoyl)benzene]sulfonyl}phenyl)methyl]-1H- 0.9510.484 pyrrolo[3,2-c]pyridine-2-carboxamideN-[(4-{[2-(methylsulfamoyl)benzene]sulfonyl}phenyl)methyl]-1H- 0.0760.202 pyrrolo[3,2-c]pyridine-2-carboxamideN-[(4-{[2-(morpholin-4-ylmethyl)benzene]sulfonyl}phenyl)methyl]-1H-0.034 0.006 pyrrolo[3,2-c]pyridine-2-carboxamide N-[(4-{[2-(morpholin-4-0.013 0.0036ylmethyl)benzene]sulfonyl}phenyl)methyl]thieno[2,3-c]pyridine-2-carboxamideN-[(4-{[2-(trifluoromethoxy)benzene]sulfonyl}phenyl)methyl]-1H- 0.0160.003 pyrrolo[3,2-c]pyridine-2-carboxamide N-[(4-{[2- 0.004 0.0028(trifluoromethoxy)benzene]sulfonyl}phenyl)methyl]thieno[2,3-c]pyridine-2-carboxamideN-[(4-{[2-(trifluoromethyl)benzene]sulfonyl}phenyl)methyl]-1H- 0.0220.025 pyrrolo[3,2-c]pyridine-2-carboxamideN-[(4-{[2-(trifluoromethyl)benzene]sulfonyl}phenyl)methyl]thieno[2,3-0.013 0.0260 c]pyridine-2-carboxamide N-[(4-{[2-fluoro-4-(1H-pyrazol-1-0.006 0.0080 yl)benzene]sulfonyl}phenyl)methyl]thieno[2,3-c]pyridine-2-carboxamide N-[(4-{[2-methoxy-4-(1H-pyrazol-1- 0.016 0.002yl)benzene]sulfonyl}phenyl)methyl]-1H-pyrrolo[3,2-c]pyridine-2-carboxamide N-[(4-{[2-methoxy-4-(1H-pyrazol-1- 0.005 0.0026yl)benzene]sulfonyl}phenyl)methyl]thieno[2,3-c]pyridine-2- carboxamideN-[(4-{[2-methoxy-4- 0.022 0.005(trifluoromethyl)benzene]sulfonyl}phenyl)methyl]-1H-pyrrolo[3,2-c]pyridine-2-carboxamide N-[(4-{[2-methoxy-4- 0.009 0.0075(trifluoromethyl)benzene]sulfonyl}phenyl)methyl]thieno[2,3-c]pyridine-2-carboxamideN-[(4-{[2-methoxy-5-(propan-2-yl)benzene]sulfonyl}phenyl)methyl]- 0.0610.012 1H-pyrrolo[3,2-c]pyridine-2-carboxamideN-[(4-{[2-methoxy-5-(propan-2- 0.009 0.0062yl)benzene]sulfonyl}phenyl)methyl]thieno[2,3-c]pyridine-2- carboxamideN-[(4-{[2-methoxy-6-(propan-2- 0.036 0.022yloxy)benzene]sulfonyl}phenyl)methyl]-1H-pyrrolo[3,2-c]pyridine-2-carboxamideN-[(4-{[2-methyl-4-(1H-pyrazol-1-yl)benzene]sulfonyl}phenyl)methyl]-0.004 0.004 1H-pyrrolo[3,2-c]pyridine-2-carboxamideN-[(4-{[3-(propan-2-yl)benzene]sulfonyl}phenyl)methyl]-1H- 0.006 0.004pyrrolo[3,2-c]pyridine-2-carboxamideN-[(4-{[3-(propan-2-yl)benzene]sulfonyl}phenyl)methyl]thieno[2,3- 0.0090.0026 c]pyridine-2-carboxamideN-[(4-{[3-(trifluoromethoxy)benzene]sulfonyl}phenyl)methyl]-1H- 0.0050.003 pyrrolo[3,2-c]pyridine-2-carboxamide N-[(4-{[3- 0.002 0.0024(trifluoromethoxy)benzene]sulfonyl}phenyl)methyl]thieno[2,3-c]pyridine-2-carboxamideN-[(4-{[3-(trifluoromethyl)benzene]sulfonyl}phenyl)methyl]-1H- 0.0090.003 pyrrolo[3,2-c]pyridine-2-carboxamideN-[(4-{[3-(trifluoromethyl)benzene]sulfonyl}phenyl)methyl]thieno[2,3-0.003 0.0010 c]pyridine-2-carboxamideN-[(4-{[3-fluoro-4-(1H-pyrazol-1-yl)benzene]sulfonyl}phenyl)methyl]-0.011 0.004 1H-pyrrolo[3,2-c]pyridine-2-carboxamideN-[(4-{[4-(dimethylcarbamoyl)benzene]sulfonyl}phenyl)methyl]-1H- 0.0270.014 pyrrolo[3,2-c]pyridine-2-carboxamideN-[(4-{[4-(propan-2-yl)benzene]sulfonyl}phenyl)methyl]thieno[2,3- 0.0060.0071 c]pyridine-2-carboxamideN-[(4-{[4-(trifluoromethyl)benzene]sulfonyl}phenyl)methyl]-1H- 0.0240.026 pyrrolo[3,2-c]pyridine-2-carboxamideN-[(4-{[4-chloro-3-(trifluoromethyl)benzene]sulfonyl}phenyl)methyl]-0.008 0.005 1H-pyrrolo[3,2-c]pyridine-2-carboxamide N-[(4-{[4-chloro-3-0.010 0.0034 (trifluoromethyl)benzene]sulfonyl}phenyl)methyl]thieno[2,3-c]pyridine-2-carboxamideN-[4-(benzenesulfonyl)phenyl]pyridine-3-carboxamide 12.038 >30N-{[3-(benzenesulfonyl)phenyl]methyl}-1H-pyrrolo[3,2-c]pyridine-2- >30 >30carboxamideN-{[4-(1H-indole-7-sulfonyl)phenyl]methyl}thieno[2,3-c]pyridine-2- 0.0030.0027 carboxamideN-{[4-(1-methyl-1H-pyrazole-4-sulfonyl)phenyl]methyl}-1H-pyrrolo[3,2-0.048 0.123 c]pyridine-2-carboxamideN-{[4-(2,3-dihydro-1,4-benzodioxine-6- 0.004 0.0027sulfonyl)phenyl]methyl}thieno[2,3-c]pyridine-2-carboxamideN-{[4-(2H-1,3-benzodioxole-5-sulfonyl)phenyl]methyl}-1H-pyrrolo[3,2-0.008 0.007 c]pyridine-2-carboxamideN-{[4-(2H-1,3-benzodioxole-5-sulfonyl)phenyl]methyl}thieno[2,3- 0.0030.0025 c]pyridine-2-carboxamideN-{[4-(5-methylthiophene-2-sulfonyl)phenyl]methyl}-1H-pyrrolo[3,2- 0.0070.013 c]pyridine-2-carboxamideN-{[4-(5-methylthiophene-2-sulfonyl)phenyl]methyl}thieno[2,3- 0.0050.0077 c]pyridine-2-carboxamideN-{[4-(benzenesulfonyl)phenyl]methyl}-[1,2,3,4]tetrazolo[1,5- 0.447 >30a]pyridine-6-carboxamideN-{[4-(benzenesulfonyl)phenyl]methyl}-[1,2,4]triazolo[4,3-a]pyridine-0.301 >10 6-carboxamideN-{[4-(benzenesulfonyl)phenyl]methyl}-1,5-naphthyridine-2- 0.875 >10carboxamideN-{[4-(benzenesulfonyl)phenyl]methyl}-1H-imidazo[4,5-c]pyridine-2- 7.0625.37 carboxamideN-{[4-(benzenesulfonyl)phenyl]methyl}-1H-pyrazolo[3,4-b]pyridine-3-1.271 >10 carboxamideN-{[4-(benzenesulfonyl)phenyl]methyl}-1H-pyrazolo[3,4-b]pyridine-5-0.070 0.051 carboxamideN-{[4-(benzenesulfonyl)phenyl]methyl}-1H-pyrrolo[2,3-b]pyridine-5-1.906 >30 carboxamideN-{[4-(benzenesulfonyl)phenyl]methyl}-1H-pyrrolo[2,3-c]pyridine-3- >10 >10carboxamideN-{[4-(benzenesulfonyl)phenyl]methyl}-1-methyl-1H-pyrazolo[3,4-1.725 >30 b]pyridine-5-carboxamideN-{[4-(benzenesulfonyl)phenyl]methyl}-1-methyl-1H-pyrrolo[3,2- >10 >30c]pyridine-2-carboxamideN-{[4-(benzenesulfonyl)phenyl]methyl}-3-(pyridin-2-yl)-1H-pyrazole-5-7.429 23.371 carboxamideN-{[4-(benzenesulfonyl)phenyl]methyl}-3-(pyridin-3-yl)-1,2-oxazole-5-0.033 >30 carboxamideN-{[4-(benzenesulfonyl)phenyl]methyl}-3-(pyridin-4-yl)-1H-pyrazole-5-3.176 21.554 carboxamideN-{[4-(benzenesulfonyl)phenyl]methyl}-3-bromo-1H-pyrrolo[3,2- 0.3067.390 c]pyridine-2-carboxamideN-{[4-(benzenesulfonyl)phenyl]methyl}-5-(pyridin-3-yl)-1,2,4- 0.312 >30oxadiazole-3-carboxamideN-{[4-(benzenesulfonyl)phenyl]methyl}-5-(pyridin-3-yl)-1H-pyrazole-3-0.023 11.825 carboxamideN-{[4-(benzenesulfonyl)phenyl]methyl}imidazo[1,2-a]pyrazine-2- 1.491 >30carboxamideN-{[4-(benzenesulfonyl)phenyl]methyl}imidazo[1,2-a]pyridine-6- 0.0210.011 carboxamideN-{[4-(benzenesulfonyl)phenyl]methyl}isoquinoline-6-carboxamide 16.08221.303 N-{[4-(benzenesulfonyl)phenyl]methyl}isoquinoline-7-carboxamide0.219 24.000N-{[4-(benzenesulfonyl)phenyl]methyl}quinazoline-6-carboxamide 16.08221.303 N-{[4-(benzenesulfonyl)phenyl]methyl}thieno[2,3-b]pyrazine-6-0.052 >30 carboxamideN-{[4-(benzenesulfonyl)phenyl]methyl}thieno[2,3-c]pyridine-2- 0.0110.012 carboxamideN-{[4-(isoquinoline-4-sulfonyl)phenyl]methyl}thieno[2,3-c]pyridine-2-0.003 0.0007 carboxamideN-{[4-(naphthalene-1-sulfonyl)phenyl]methyl}thieno[2,3-c]pyridine-2-0.002 0.0005 carboxamideN-{[4-(phenoxathiine-4-sulfonyl)phenyl]methyl}-1H-pyrrolo[3,2- 0.0050.0009 c]pyridine-2-carboxamideN-{[4-(phenoxathiine-4-sulfonyl)phenyl]methyl}thieno[2,3-c]pyridine-0.004 0.0017 2-carboxamideN-{[4-(phenylmethane)sulfonylphenyl]methyl}-1H-pyrrolo[3,2- 0.029 0.3015c]pyridine-2-carboxamideN-{[4-(pyridine-3-sulfonyl)phenyl]methyl}-1H-pyrrolo[3,2-c]pyridine-2-0.021 0.048 carboxamideN-{[4-(quinoline-3-sulfonyl)phenyl]methyl}thieno[2,3-c]pyridine-2- 0.0030.0008 carboxamideN-{[4-(quinoline-6-sulfonyl)phenyl]methyl}thieno[2,3-c]pyridine-2- 0.0030.0009 carboxamideN-{[4-(quinoline-8-sulfonyl)phenyl]methyl}thieno[2,3-c]pyridine-2- 0.0060.0025 carboxamideN-{2-[4-(benzenesulfonyl)phenyl]ethyl}-1H-pyrrolo[3,2-c]pyridine-2-0.410 9.1 carboxamideN-({4-[(1H-indazol-6-yl)sulfamoyl]phenyl}methyl)-1H-pyrrolo[3,2- 0.1355.44 c]pyridine-2-carboxamideN-({4-[(1-oxo-1H-isochromen-5-yl)sulfamoyl]phenyl}methyl)-1H- 0.008 2.27pyrrolo[3,2-c]pyridine-2-carboxamideN-({4-[(2,3-dihydro-1,4-benzodioxin-6-yl)sulfamoyl]phenyl}methyl)-1H- >10 >10pyrrolo[3,2-c]pyridine-2-carboxamideN-({4-[(2-acetylphenyl)sulfamoyl]phenyl}methyl)-1H-pyrrolo[3,2- 0.0050.005 c]pyridine-2-carboxamideN-({4-[(2-methoxy-6-methylphenyl)sulfamoyl]phenyl}methyl)-1H- 0.006 12.4pyrrolo[3,2-c]pyridine-2-carboxamideN-({4-[(2-methoxyphenyl)sulfamoyl]phenyl}methyl)-1H-pyrrolo[3,2- 0.0892.150 c]pyridine-2-carboxamideN-({4-[(2-phenoxyphenyl)sulfamoyl]phenyl}methyl)-1H-pyrrolo[3,2- 4.01912.000 c]pyridine-2-carboxamideN-({4-[(2-propoxyphenyl)sulfamoyl]phenyl}methyl)-1H-pyrrolo[3,2- 0.0520.100 c]pyridine-2-carboxamideN-({4-[(3-methoxy-2-methylphenyl)sulfamoyl]phenyl}methyl)-1H- 0.0300.006 pyrrolo[3,2-c]pyridine-2-carboxamideN-({4-[(4-chloro-2-methoxy-5-methylphenyl)sulfamoyl]phenyl}methyl)-7.835 18.322 1H-pyrrolo[3,2-c]pyridine-2-carboxamideN-({4-[(4-ethoxy-2-fluorophenyl)sulfamoyl]phenyl}methyl)-1H- 0.154 1.600pyrrolo[3,2-c]pyridine-2-carboxamideN-({4-[(4-fluoro-2-methoxyphenyl)sulfamoyl]phenyl}methyl)-1H- 3.138 >30pyrrolo[3,2-c]pyridine-2-carboxamideN-({4-[(4-methoxy-2-methylphenyl)sulfamoyl]phenyl}methyl)-1H- 1.451 >30pyrrolo[3,2-c]pyridine-2-carboxamideN-({4-[(5,6,7,8-tetrahydronaphthalen-1-yl)sulfamoyl]phenyl}methyl)- >30 >301H-pyrrolo[3,2-c]pyridine-2-carboxamideN-({4-[(5-chloro-2-methoxyphenyl)sulfamoyl]phenyl}methyl)-1H- 0.19717.984 pyrrolo[3,2-c]pyridine-2-carboxamideN-({4-[(5-fluoro-2-methoxyphenyl)sulfamoyl]phenyl}methyl)-1H- 0.232 >30pyrrolo[3,2-c]pyridine-2-carboxamideN-({4-[(5-methoxy-2-methylphenyl)sulfamoyl]phenyl}methyl)-1H- 0.05113.018 pyrrolo[3,2-c]pyridine-2-carboxamideN-({4-[(quinolin-8-yl)sulfamoyl]phenyl}methyl)-1H-pyrrolo[3,2- 0.0751.478 c]pyridine-2-carboxamideN-[(4-{[2-(2-hydroxyethoxy)phenyl]sulfamoyl}phenyl)methyl]-1H- 19.61123.854 pyrrolo[3,2-c]pyridine-2-carboxamideN-[(4-{[2-(hydroxymethyl)phenyl]sulfamoyl}phenyl)methyl]-1H- 0.030 0.006pyrrolo[3,2-c]pyridine-2-carboxamideN-[(4-{[2-(morpholin-4-yl)phenyl]sulfamoyl}phenyl)methyl]-1H- 0.0190.017 pyrrolo[3,2-c]pyridine-2-carboxamideN-[(4-{[2-(piperidin-1-yl)phenyl]sulfamoyl}phenyl)methyl]-1H- 0.0720.008 pyrrolo[3,2-c]pyridine-2-carboxamideN-[(4-{[2-(propan-2-yloxy)phenyl]sulfamoyl}phenyl)methyl]-1H- 0.0030.001 pyrrolo[3,2-c]pyridine-2-carboxamideN-[(4-{[2-(trifluoromethoxy)benzene]sulfonamido}phenyl)methyl]-1H- 0.0030.001 pyrrolo[3,2-c]pyridine-2-carboxamideN-[(4-{[2-(trifluoromethoxy)phenyl]sulfamoyl}phenyl)methyl]-1H- 0.0060.001 pyrrolo[3,2-c]pyridine-2-carboxamide N-[(4-{[2-methoxy-5- 0.00050.0016 (trifluoromethyl)phenyl]sulfamoyl}phenyl)methyl]-1H-pyrrolo[3,2-c]pyridine-2-carboxamide N-[(4-{[4-chloro-2- 0.002 0.002(trifluoromethoxy)phenyl]sulfamoyl}phenyl)methyl]-1H-pyrrolo[3,2-c]pyridine-2-carboxamideN-[(4-{8-oxa-3-azabicyclo[3.2.1]octane-3-sulfonyl}phenyl)methyl]-1H-0.008 0.003 pyrrolo[3,2-c]pyridine-2-carboxamideN-[(4-{8-oxa-3-azabicyclo[3.2.1]octane-3- 0.004 0.003sulfonyl}phenyl)methyl]imidazo[1,2-a]pyridine-6-carboxamideN-[(4-{8-oxa-3-azabicyclo[3.2.1]octane-3- 0.015 0.003sulfonyl}phenyl)methyl]thieno[2,3-c]pyridine-2-carboxamideN-[(4-benzamidophenyl)methyl]-1H-pyrrolo[3,2-c]pyridine-2- 0.019 0.004carboxamideN-[(4-benzenesulfonamidophenyl)methyl]-1H-pyrrolo[3,2-c]pyridine-2-0.011 0.005 carboxamideN-[4-(piperidine-1-sulfonyl)phenyl]-1H-pyrrolo[3,2-c]pyridine-2- 0.0080.006 carboxamideN-[4-(piperidine-1-sulfonyl)phenyl]-2-(pyridin-3-yloxy)acetamide 0.00110.0066 N-[4-(piperidine-1-sulfonyl)phenyl]-3-(pyridin-3-yl)propanamide0.003 0.007N-{[1-(benzenesulfonyl)piperidin-4-yl]methyl}-1H-pyrrolo[3,2- 0.0150.009 c]pyridine-2-carboxamideN-{[4-(piperidine-1-sulfonyl)phenyl]methyl}-[1,2,3,4]tetrazolo[1,5-0.003 0.009 a]pyridine-7-carboxamideN-{[4-(piperidine-1-sulfonyl)phenyl]methyl}-1,3-benzothiazole-6- 0.0090.010 carboxamideN-{[4-(piperidine-1-sulfonyl)phenyl]methyl}-1,6-naphthyridine-2- 0.0120.010 carboxamideN-{[4-(piperidine-1-sulfonyl)phenyl]methyl}-1H-1,3-benzodiazole-5- 0.0210.010 carboxamideN-{[4-(piperidine-1-sulfonyl)phenyl]methyl}-1H-imidazo[1,2- 0.00080.0110 b]pyrazole-5-carboxamideN-{[4-(piperidine-1-sulfonyl)phenyl]methyl}-1H-indazole-5- 0.018 0.016carboxamide N-{[4-(piperidine-1-sulfonyl)phenyl]methyl}-1H-pyrazolo[3,4-0.017 0.033 b]pyridine-5-carboxamideN-{[4-(piperidine-1-sulfonyl)phenyl]methyl}-1H-pyrrolo[2,3-c]pyridine-0.004 0.054 2-carboxamideN-{[4-(piperidine-1-sulfonyl)phenyl]methyl}-1H-pyrrolo[3,2-c]pyridine-0.023 0.200 2-carboxamideN-{[4-(piperidine-1-sulfonyl)phenyl]methyl}furo[3,2-c]pyridine-2- 0.0170.286 carboxamideN-{[4-(piperidine-1-sulfonyl)phenyl]methyl}imidazo[1,2-a]pyridine-6-0.018 1.160 carboxamideN-{[4-(piperidine-1-sulfonyl)phenyl]methyl}imidazo[1,2-a]pyridine-7- >0.1 >0.5carboxamideN-{[4-(piperidine-1-sulfonyl)phenyl]methyl}pyridine-3-carboxamide 0.0390.64 N-{[4-(piperidine-1-sulfonyl)phenyl]methyl}thieno[2,3-b]pyridine-2-6.146 14.000 carboxamideN-{[4-(piperidine-1-sulfonyl)phenyl]methyl}thieno[3,2-c]pyridine-2-0.886 10 carboxamideN-{1-[4-(piperidine-1-sulfonyl)phenyl]ethyl}-1H-pyrrolo[3,2-c]pyridine-0.020 0.007 2-carboxamideN-{[4-(benzenesulfonyl)phenyl]methyl}-5,6,7,8-tetrahydro-1,6- 0.544 >2naphthyridine-6-carboxamideN-{[4-(benzenesulfonyl)phenyl]methyl}-5H,6H,7H-pyrrolo[3,4- 0.020 >2b]pyridine-6-carboxamideN-{[4-(benzenesulfonyl)phenyl]methyl}-1H,4H,5H,6H,7H-pyrazolo[4,3- >2 >2c]pyridine-5-carboxamideN-{[4-(benzenesulfonyl)phenyl]methyl}-5H,6H,7H,8H-pyrido[4,3- >2 >2d]pyrimidine-6-carboxamideN-{[4-(benzenesulfonyl)phenyl]methyl}-1H,4H,5H,6H,7H-imidazo[4,5- >2 >2c]pyridine-5-carboxamideN-{[4-(benzenesulfonyl)phenyl]methyl}-4H,5H,6H,7H-[1,2]oxazolo[4,3- >2 >2c]pyridine-5-carboxamide

Assay Example 3 In-Vitro Cell Proliferation Assay

U251 cells were seeded in 96-well plates at 1.25×103 cells/well in 180μL of culture medium (10% FBS, 1% Pen/Strep Amphotecricin B, RPMI-51640) with and without the addition of either _-nicotinamidemononucleotide (NMN) or nicotinamide (NAM). After overnight incubationat 37° C. and 5% CO2, the compound titrations were performed in aseparate dilution plate by serially diluting the compounds in DMSO tomake a 1000× stock. The compounds were then further diluted to 10× finalconcentration in culture media, whereupon 20 μL of each dilution wasadded to the plated cells with controls (e.g. DMSO and blank) to make afinal volume of 5 200 μL. The final DMSO concentration in each well was0.1%. The plates were then incubated for 72 hours at 37° C. in a 5% CO2incubator. The number of viable cells was then assessed usingsulforhodamine B (SRB) assay. Cells were fixed at 4° C. for 1 hour withthe addition of 50 μL 30% trichloroacetic acid (TCA) to make a finalconcentration of 6% 10 TCA. The plates were washed four times with H2Oand allowed to dry for at least 1 hour, whereupon 100 μL of a 4% SRB in1% acetic acid solution was added to each well and incubated at roomtemperature for at least 30 minutes. The plates were then washed threetimes with 1% acetic acid, dried, and treated with 100 μL of 10 mMTris-Base solution. The plates were then read in a microplate reader atan absorbance of 570 nm. 15 Background was generated on a separate platewith media only.

Method for Determining % Inhibition

First, the signals from the background plate are averaged, then thebackground was subtracted from the test plates. The compound-treatedcells were then assayed for % 20 inhibition by using the followingformula:

% Inh=100−100*x/y

wherein x denotes the average signal of the compound-treated cells and ydenotes the average signal of the DMSO-treated cells.

25 Formula for Cetermining IC50 Values:

IC50=10̂(LOG 10(X)+(((50-% Inh at Cmpd Concentration 1)/(XXYY)*(LOG10(X)-LOG 10(Y))))

wherein X denotes the compound concentration 1, Y denotes the compoundconcentration 2, XX denotes the % inhibition at compound concentration 1(X), and YY 30 denotes the % inhibition at compound concentration 2 (Y).

Table 4 below shows U251-values for some compounds.

U251 Chemical name IC50 (uM)N-{[4-(benzenesulfonyl)phenyl]methyl}thieno[3,2-b]pyridine-2-carboxamide >2N-{[4-(benzenesulfonyl)phenyl]methyl}imidazo[1,5-a]pyridine-6-carboxamide >2 N-{[4-(benzenesulfonyl)phenyl]methyl}-1H-pyrrolo[3,2-c]pyridine-2-carboxamide 0.040N-{[5-(benzenesulfonyl)pyridin-2-yl]methyl}-1H-pyrrolo[3,2-c]pyridine-2-carboxamide 0.035N-{[4-(benzenesulfonyl)phenyl]methyl}-imidazo[1,2-a]pyrazine-6-carboxamide >2N-{[4-(benzenesulfonyl)phenyl]methyl}furo[3,2- b]pyridine-2-carboxamide0.545 N-{[6-(benzenesulfonyl)pyridin-3-yl]methyl}-1H-pyrrolo[3,2-c]pyridine-2-carboxamide >2 N-{[4-(piperazine-1-sulfonyl)phenyl]methyl}thieno[2,3- c]pyridine-2-carboxamide 0.405N-{[4-(piperazine- 1-sulfonyl)phenyl]methyl}imidazo[1,2-a]pyridine-6-carboxamide 0.556 N-{[4-(3-aminopyrrolidine-1-sulfonyl)phenyl]methyl}thieno[2,3- c]pyridine-2-carboxamidehydrochloride 0.31 N-{[4-(3-aminopyrrolidine-1-sulfonyl)phenyl]methyl}furo[2,3- c]pyridine-2-carboxamidehydrochloride 1.85 N-({4-[(3,5-difluorobenzene)sulfinyl]phenyl}methyl)imidazo[1,2-a]pyridine-6-carboxamide 0.0066

Xenograft Studies:

C.B-17-Igh-1b-Prkdc^(scid) mice (female) were injected s.c. with 5×10⁶A2780 cells (NCI) in the left flank. 10-12 days later when tumorsreached 100-200 mm3 in size, mice were randomized into treatment groupsof 8 mice per group including vehicle control and reference standardgroups. The compounds were formulated in 60:30:10 PEG-400:D5W: Ethanoland administered p.o., at the dose volume of 10 ml/kg BID for a durationof 5 or 10 days. The dose used for efficacy was selected from the MTD(Maximum Tolerated Dose) study. Mice were weighed and tumors measuredusing vernier calipers every alternate day. Tumor volume was calculatedaccording to the formula (length×width)/2. All animal work was approvedby the Institutional Animal Care and Use Committee of BiologicalResource Centre, Singapore.

The compound N-[(4-{[2-(trifluoromethoxy)phenyl]sulfamoyl}phenyl)methyl]-1H-pyrrolo[3,2-c]pyridine-2-carboxamide produced tumor stasis.

The following compounds produced tumor regression:

-   N-{[4-(benzenesulfonyl)phenyl]methyl}imidazo[1,2-a]pyridine-6-carboxamide;-   N-{[4-(benzenesulfonyl)phenyl]methyl}thieno[2,3-c]pyridine-2-carboxamide;-   N-{[4-(benzenesulfonyl)phenyl]methyl}-1H-pyrrolo[3,2-c]pyridine-2-carboxamide-   N-({4-[(4-fluorobenzene)sulfonyl]phenyl}methyl)-1H-pyrrolo[3,2-c]pyridine-2-carboxamide;-   N-({4-[(4-fluorobenzene)sulfonyl]phenyl}methyl)imidazo[1,2-a]pyridine-6-carboxamide;-   N-({4-[(4-acetylbenzene)sulfonyl]phenyl}methyl)-1H-pyrrolo[3,2-c]pyridine-2-carboxamide;-   N-[(4-{[2-(trifluoromethoxy)benzene]sulfonyl}phenyl)methyl]-1H-pyrrolo[3,2-c]pyridine-2-carboxamide;-   N-({4-[(3-chlorobenzene)sulfonyl]phenyl}methyl)-1H-pyrrolo[3,2-c]pyridine-2-carboxamide.

The following compounds delayed tumor growth;

-   N-{[4-(pyridine-3-sulfonyl)phenyl]methyl}-1H-pyrrolo[3,2-c]pyridine-2-carboxamide.-   N-[(4-{[2-methoxy-4-(1H-pyrazol-1-yl)benzene]sulfonyl}phenyl)methyl]-1H-pyrrolo[3,2-c]pyridine-2-carboxamide

While the present invention has been described in conjunction with thespecific embodiments set forth above, many alternatives, modificationsand other variations thereof will be apparent to those of ordinary skillin the art. All such alternatives, modifications and variations areintended to fall within the spirit and scope of the present invention.

LENGTHY TABLES The patent application contains a lengthy table section.A copy of the table is available in electronic form from the USPTO website(http://seqdata.uspto.gov/?pageRequest=docDetail&DocID=US20190105307A1).An electronic copy of the table will also be available from the USPTOupon request and payment of the fee set forth in 37 CFR 1.19(b)(3).

1-20. (canceled)
 21. A compound of formula IIB or a pharmaceuticallyacceptable salt thereof:

wherein: R is bicyclic heteroaryl comprising 1, 2, 3, or 4 heteroatom(s)independently selected from N, S, and O, wherein said heteroaryl may besubstituted by one or more substituents selected from the groupconsisting of amino, oxo, and halo; and wherein said heteroaryl cancomprise one or more N-oxide(s) formed with a N atom member of saidheteroaryl; R¹ is heteroaryl, wherein: (i) said heteroaryl isunsubstituted or substituted with 1, 2, 3, 4, or 5 substituents whichcan be the same or different and are independently selected from thegroup consisting of: deuterium, halo, hydroxy, hydroxyalkyl, cyano,—(CH₂)_(m)NR^(a)R^(b), oxo, alkyl, cyanoalkyl, haloalkyl, alkoxy,haloalkoxy, alkoxyalkyl-, alkenyl, alkynyl, alkynylalkoxy, —CONH₂,—S-alkyl, —C(O)NH(alkyl), —C(O)N(alkyl)₂, —C(O)NH(cycloalkyl),—C(O)NH(aryl), —C(O)N(aryl)₂, arylalkyl-, arylalkoxy-, aryloxy-,cycloalkyl, heterocycloalkyl, aryl, (heterocycloalkyl)alkyl-,(heterocycloalkyl)alkoxy, —C(O)heterocycloalkyl, heteroaryl,(heteroaryl)alkyl-, —S(O)₂-alkyl, —S(O)₂-aryl, —S(O)₂—CH_(z)F_(3−z),—C(O)alkyl, —N(R⁵)—C(O)-alkyl, —N(R⁵)—C(O)-aryl, —S(O)₂NH₂,—S(O)₂NH(alkyl), —S(O)₂N(alkyl)₂, —N(H)S(O)₂(alkyl), and methylenedioxy,wherein each of said cycloalkyl, heterocycloalkyl, aryl, or heteroarylmay be substituted by one or more halo, cyano, alkyl, and alkoxy; and(ii) said heteroaryl may optionally additionally be fused withindependently selected heterocycloalkyl or cycloalkyl to form a bicyclicor tricyclic group that may be substituted by one or more halo, cyano,alkyl, and alkoxy; R² and R³ can be independently selected from thegroup consisting of H and deuterium; R⁵ is H, alkyl, or arylalkyl; R^(a)and R^(b) are independently selected from the group consisting of H,alkyl, alkoxy, alkoxyalkyl, and haloalkyl; m is 0, 1, 2, 3, 4, 5, or 6;and z is 0, 1, or
 2. 22. The compound of claim 21, wherein R is selectedfrom 9- to 10-membered bicyclic heteroaryl groups containing 1, 2, 3, or4 heteroatoms independently selected from N, S, and O.
 23. The compoundof claim 21, wherein R is selected from the group consisting of:benzothiazole, dihydronaphthyridine, dihydropyridopyrimidine,dihydropyrrolopyridine, furopyridine, imidazopyrazine, imidazopyrazole,imidazopyridine, imidazopyrimidine, indazole, indole, isoquinoline,naphthyridine, pyrazolopyridine, pyrrolopyridine, tetrazolopyridine,tetrahydroimidazopyridine, tetrahydropyrazolopyridine, thiazolopyridine,and thienopyridine.
 24. The compound of claim 21, wherein R is selectedfrom the group consisting of: 1H-pyrazolo[3,4-b]pyridine;1,4,6,7-Tetrahydro-pyrazolo[4,3-c]pyridine;7,8-Dihydro-5H-pyrido[4,3-d]pyrimidine;5,7-Dihydro-pyrrolo[3,4-b]pyridine; 7,8-Dihydro-5H-[1,6]naphthyridine;1,4,6,7-Tetrahydro-imidazo[4,5-c]pyridine;1,8a-dihydroimidazo[1,2-a]pyridine; thieno[3,2-c]pyridine;1H-imidazo[1,2-b]pyrazole; furo[2,3-c]pyridine;1H-pyrrolo[3,2-c]pyridine; thieno[2,3-b]pyridine;imidazo[1,2-a]pyrimidine; furo[2,3-c]pyridine; isoquinoline;1H-indazole; imidazo[1,2-a]pyridine; thieno[2,3-c]pyridine;furo[2,3-c]pyridine; 1H-pyrrolo[2,3-c]pyridine; imidazo[1,2-a]pyrazine;1,3-benzothiazole; benzo[d]thiazole; 1H-pyrrolo[2,3-b]pyridine;[1,3]thiazolo[5,4-c]pyridine; [1,2,3,4]tetrazolo[1,5-a]pyridine;1,5-naphthyridine; 1H-indole; 1H-imidazo[4,5-c]pyridine; and1,6-naphthyridine.
 25. The compound of claim 21, wherein R issubstituted at a position adjacent to a nitrogen atom on its cycle. 26.The compound of claim 21, wherein R¹ is unsubstituted or substituted 5-to 10-membered monocyclic or bicyclic heteroaryl comprising 1, 2, 3, or4 heteroatom(s) selected from N, S, or O.
 27. The compound of claim 21,wherein R¹ is selected from the group consisting of: 6-methoxypyridine;1-(3-chlorophenyl)-1H-pyrazole; 1-(4-fluorophenyl)-1H-pyrazole;1-(propan-2-yl)-1H-pyrazole; 1,3-thiazole; 1,4-dimethyl-1H-imidazole;1,5-dimethyl-1H-imidazole; 1-benzothiophene; 1H-indole;1-methyl-1H-1,3-benzodiazole; 1-methyl-1H-indazole; 1-methyl-1H-indole;1-methyl-1H-pyrazole; 1-methyl-3-(trifluoromethyl)-1H-pyrazole;1-methyl-5-(trifluoromethyl)-1H-pyrazole; 1-propyl-1H-pyrazole;2-(3-fluorophenyl)-1,3-thiazole; 2-(dimethylamino)pyrimidine;2-(morpholin-4-yl)pyridine; 2-(morpholin-4-yl)pyridine;2-(pyrrolidin-1-yl)-1,3-thiazole;2-(trifluoromethyl)imidazo[1,2-a]pyridine; 2-(trifluoromethyl)pyridine;2,6-dimethoxypyridine; 2-[ethyl(methyl)amino]-1,3-thiazole;2-methyl-1,3-thiazole; 2-methyl-2H-indazole; 2-methylpyridine;3-chloro-2-(morpholin-4-yl)pyridine; 4-(trifluoromethyl)pyridine;4-methylpyridine; 4-methylthiophene; 5-(dimethylamino)pyrazine;5-(pyrrolidin-1-yl)pyridine; 5-(trifluoromethyl)pyridine;5-chloropyridine; 5-fluoro-6-methylpyridine; 5-fluoropyridine;5H,6H,7H,8H,9H-imidazo[1,2-a]azepine; 5-hydroxy-1-methyl-1H-indazole;5-methoxypyridine; 5-methylpyridine; 5-methylthiophene;6-(1H-pyrazol-1-yl)pyridine; 6-(3,4-difluorophenyl)pyridine;6-(4-methylpiperazin-1-yl)pyridine; 6-(dimethylamino)pyridine;6-(morpholin-4-yl)pyridine; 6-(trifluoromethyl)pyridine;6-chloroimidazo[1,2-a]pyridine; 6-methoxypyridine; 6-methylpyrazine;6-methylpyridine; b6-chloroimidazo[1,2-a]pyridine;dimethyl-1,3-thiazole; furan; isoquinoline; and pyridine.
 28. Thecompound of claim 21 wherein R¹ is heteroaryl, wherein said heteroarylis unsubstituted or substituted with 1, 2, 3, 4, or 5 substituents whichcan be the same or different and are independently selected from thegroup consisting of: halo, hydroxy, hydroxyalkyl, cyano, alkyl, alkynyl,alkynylalkoxy, alkoxyalkyl, alkoxy, haloalkyl, haloalkoxy,—C(O)NH(alkyl), —C(O)NH(cycloalkyl), —C(O)N(alkyl)₂, arylalkoxy-,aryloxy-, cycloalkyl, heterocycloalkyl, aryl, (heterocycloalkyl)alkyl-,(heterocycloalkyl)alkoxy-, —C(O)heterocycloalkyl, heteroaryl,(heteroaryl)alkyl-, —S(O)₂-alkyl, —S-alkyl, —C(O)alkyl, —S(O₂)NH₂,—S(O₂)NH(alkyl), —S(O₂)N(alkyl)₂, and —N(H)(SO₂)(alkyl), wherein each ofsaid cycloalkyl, heterocycloalkyl, aryl, or heteroaryl may besubstituted by one or more halo, cyano, alkyl, and alkoxy.
 29. Thecompound of claim 21, wherein R¹ is heteroaryl, wherein said heteroarylis unsubstituted or substituted with 1, 2, 3, 4, or 5 substituents whichcan be the same or different and are independently selected from thegroup consisting of: halo, haloalkyl, and haloalkoxy.
 30. The compoundof claim 29, wherein haloalkyl is —CH_(z)F_(3−z), or —CH₂CH_(z)F_(3−z),and z is 0, 1 or
 2. 31. The compound of claim 29, wherein haloalkoxy is—OCH_(z)F_(3−z), and z is 0, 1 or
 2. 32. The compound of claim 29,wherein halo is F.
 33. A compound selected from the group consisting of:N-({4-[1-(3-chlorophenyl)-1H-pyrazole-4-sulfonyl]phenyl}methyl)-1H-pyrazolo[3,4-b]pyridine-5-carboxamideN-{[4-(dimethyl-1,3-thiazole-5-sulfonyl)phenyl]methyl}-1H-pyrazolo[3,4-b]pyridine-5-carboxamideN-({4-[1-methyl-5-(trifluoromethyl)-1H-pyrazole-4-sulfonyl]phenyl}methyl)imidazo[1,2-a]pyrimidine-6-carboxamideN-({4-[6-(trifluoromethyl)pyridine-3-sulfonyl]phenyl}methyl)thieno[2,3-c]pyridine-2-carboxamideN-{[4-(2-methyl-2H-indazole-6-sulfonyl)phenyl]methyl}-1H-pyrazolo[3,4-b]pyridine-5-carboxamideN-({4-[6-(trifluoromethyl)pyridine-2-sulfonyl]phenyl}methyl)furo[2,3-c]pyridine-2-carboxamideN-({4-[6-(trifluoromethyl)pyridine-2-sulfonyl]phenylmethyl)-1H-pyrazolo[3,4-b]pyridine-5-carboxamideN-{[4-(1-methyl-1H-indazole-7-sulfonyl)phenyl]methyl}furo[2,3-c]pyridine-2-carboxamideN-{[4-(5-chloro-3-methylpyridine-2-sulfonyl)phenyl]methyl}imidazo[1,2-a]pyrimidine-6-carboxamideN-{[4-(isoquinoline-4-sulfonyl)phenyl]methyl}thieno[2,3-c]pyridine-2-carboxamideN-({4-[6-(morpholin-4-yl)pyridine-3-sulfonyl]phenyl}methyl)-1H-pyrazolo[3,4-b]pyridine-5-carboxamideN-{[4-(1-methyl-1H-indazole-5-sulfonyl)phenyl]methyl}imidazo[1,2-a]pyridine-6-carboxamideN-{[4-(1-propyl-1H-pyrazole-4-sulfonyl)phenyl]methyl}-1H-pyrazolo[3,4-b]pyridine-5-carboxamideN-({4-[2-(trifluoromethyl)imidazo[1,2-a]pyridine-6-sulfonyl]phenyl}methyl)-1H-pyrazolo[3,4-b]pyridine-5-carboxamideN-[(4-{6-chloroimidazo[1,2-a]pyridine-3-sulfonyl}phenyl)methyl]imidazo[1,2-a]pyrimidine-6-carboxamideN-{[4-(6-methoxypyridine-2-sulfonyl)phenyl]methyl}furo[2,3-c]pyridine-2-carboxamideN-({4-[6-(dimethylamino)pyridine-3-sulfonyl]phenyl}methyl)-1H-pyrrolo[3,2-c]pyridine-2-carboxamideN-{[4-(1-methyl-1H-indazole-4-sulfonyl)phenyl]methyl}imidazo[1,2-a]pyrimidine-6-carboxamideN-{[4-(2-methylpyridine-3-sulfonyl)phenyl]methyl}thieno[2,3-c]pyridine-2-carboxamideN-{[4-(5-methylthiophene-2-sulfonyl)phenyl]methyl}-1H-pyrrolo[3,2-c]pyridine-2-carboxamideN-{[4-(1-methyl-1H-indazole-6-sulfonyl)phenyl]methyl}thieno[2,3-c]pyridine-2-carboxamideN-{[4-(1-methyl-1H-indazole-6-sulfonyl)phenyl]methyl}imidazo[1,2-a]pyridine-6-carboxamideN-({4-[6-(dimethylamino)pyridine-3-sulfonyl]phenyl}methyl)imidazo[1,2-a]pyrimidine-6-carboxamideN-[(4-{2-[ethyl(methyl)amino]-1,3-thiazole-5-sulfonyl}phenyl)methyl]thieno[2,3-c]pyridine-2-carboxamideN-{[4-(1-propyl-1H-pyrazole-4-sulfonyl)phenyl]methyl}-1H-pyrrolo[3,2-c]pyridine-2-carboxamideN-{[4-(2-methyl-2H-indazole-6-sulfonyl)phenyl]methyl}thieno[2,3-c]pyridine-2-carboxamideN-({4-[2-(dimethylamino)pyrimidine-5-sulfonyl]phenyl}methyl)-1H-pyrrolo[3,2-c]pyridine-2-carboxamideN-({4-[2-(dimethylamino)pyrimidine-5-sulfonyl]phenyl}methyl)-1H-pyrazolo[3,4-b]pyridine-5-carboxamideN-({4-[1-(4-fluorophenyl)-1H-pyrazole-4-sulfonyl]phenylmethyl)thieno[2,3-c]pyridine-2-carboxamideN-{[4-(4-methylpyridine-3-sulfonyl)phenyl]methyl}-1H-pyrrolo[3,2-c]pyridine-2-carboxamideN-{[4-(2-methyl-2H-indazole-5-sulfonyl)phenyl]methylimidazo[1,2-a]pyrimidine-6-carboxamideN-{[4-[1,3-thiazole-2-sulfonyl)phenyl]methyl}thieno[2,3-c]pyridine-2-carboxamideN-{[4-(6-methylpyrazine-2-sulfonyl)phenyl]methyl}thieno[2,3-c]pyridine-2-carboxamideN-({4-[2-(3-fluorophenyl)-1,3-thiazole-4-sulfonyl]phenylmethyl)furo[2,3-c]pyridine-2-carboxamideN-({4-[5-(trifluoromethyl)pyridine-2-sulfonyl]phenyl}methyl)thieno[2,3-c]pyridine-2-carboxamideN-[4-(5-chloro-3-methylpyridine-2-sulfonyl)phenyl]methyl}furo[2,3-c]pyridine-2-carboxamideN-({4-[6-(trifluoromethyl)pyridine-2-sulfonyl]phenyl}methyl)thieno[2,3-c]pyridine-2-carboxamideN-({4-[1-(3-chlorophenyl)-1H-pyrazole-4-sulfonyl]phenyl{methyl)imidazo[1,2-a]pyridine-6-carboxamideN-({4-[2-(3-fluorophenyl)-1,3-thiazole-4-sulfonyl]phenyl{methyl)imidazo[1,2-a]pyrimidine-6-carboxamideN-({4-[5-(trifluoromethyl)pyridine-3-sulfonyl]phenyl}methyl)-1H-pyrazolo[3,4-b]pyridine-5-carboxamideN-{[4-(dimethyl-1,3-thiazole-5-sulfonyl)phenyl]methyl}imidazo[1,2-a]pyrimidine-6-carboxamideN-{[4-(6-methylpyridine-3-sulfonyl)phenyl]methyl}-1H-pyrazolo[3,4-b]pyridine-5-carboxamideN-({4-[5-(pyrrolidin-1-yl)pyridine-3-sulfonyl]phenyl}methyl)furo[2,3-c]pyridine-2-carboxamideN-({4-[5-(trifluoromethyl)pyridine-2-sulfonyl]phenyl}methyl)imidazo[1,2-a]pyrimidine-6-carboxamideN-{[4-(1,3-thiazole-2-sulfonyl)phenyl]methyl}imidazo[1,2-a]pyridine-6-carboxamideN-{[4-(6-methylpyrazine-2-sulfonyl)phenyl]methyl}imidazo[1,2-a]pyrimidine-6-carboxamideN-{[4-(1-methyl-1H-indazole-7-sulfonyl)phenyl]methyl}imidazo[1,2-a]pyridine-6-carboxamideN-{[4-(1H-indole-7-sulfonyl)phenyl]methyl}thieno[2,3-c]pyridine-2-carboxamideN-({4-[6-(1H-pyrazol-1-yl)pyridine-3-sulfonyl]phenylmethyl)imidazo[1,2-a]pyridine-6-carboxamideN-({4-[2-(3-fluorophenyl)-1,3-thiazole-4-sulfonyl]phenyl}methyl)-1H-pyrrolo[3,2-c]pyridine-2-carboxamideN-{[4-(1-benzothiophene-7-sulfonyl)phenyl]methyl}furo[2,3-c]pyridine-2-carboxamideN-{[4-(6-methylpyrazine-2-sulfonyl)phenyl]methyl}-1H-pyrazolo[3,4-b]pyridine-5-carboxamideN-({4-[2-(morpholin-4-yl)pyridine-3-sulfonyl]phenyl}methyl)imidazo[1,2-a]pyrimidine-6-carboxamideN-{[4-(isoquinoline-4-sulfonyl)phenyl]methyl}imidazo[1,2-a]pyridine-6-carboxamideN-{[4-(1-methyl-1H-1,3-benzodiazole-6-sulfonyl)phenyl]methyl}imidazo[1,2-a]pyrimidine-6-carboxamideN-({4-[5-(pyrrolidin-1-yl)pyridine-3-sulfonyl]phenyl}methyl)-1H-pyrrolo[3,2-c]pyridine-2-carboxamideN-({4-[4-(trifluoromethyl)pyridine-2-sulfonyl]phenyl}methyl)thieno[2,3-c]pyridine-2-carboxamideN-({4-[6-(3,4-difluorophenyl)pyridine-2-sulfonyl]phenyl}methyl)thieno[2,3-c]pyridine-2-carboxamideN-{[4-(5-fluoro-6-methylpyridine-2-sulfonyl)phenyl]methyl}thieno[2,3-c]pyridine-2-carboxamideN-{[4-(isoquinoline-4-sulfonyl)phenyl]methyl}imidazo[1,2-a]pyrimidine-6-carboxamideN-({4-[6-(trifluoromethyl)pyridine-2-sulfonyl]phenyl}methyl)imidazo[1,2-a]pyrimidine-6-carboxamideN-{[4-(1-methyl-1H-indazole-6-sulfonyl)phenyl]methyl}imidazo[1,2-a]pyrimidine-6-carboxamideN-({4-[2-(trifluoromethyl)imidazo[1,2-a]pyridine-6-sulfonyl]phenyl}methyl)thieno[2,3-c]pyridine-2-carboxamideN-{[4-(2-methylpyridine-3-sulfonyl)phenyl]methyl}imidazo[1,2-a]pyrimidine-6-carboxamideN-({4-[6-(3,4-difluorophenyl)pyridine-2-sulfonyl]phenyl}methyl)-1H-pyrazolo[3,4-b]pyridine-5-carboxamideN-({4-[5-(pyrrolidin-1-yl)pyridine-3-sulfonyl]phenyl}methyl)imidazo[1,2-a]pyridine-6-carboxamideN-{[4-(5-chloro-3-methylpyridine-2-sulfonyl)phenyl]methyl}thieno[2,3-c]pyridine-2-carboxamideN-({4-[2-(pyrrolidin-1-yl)-1,3-thiazole-5-sulfonyl]phenyl}methyl)-1H-pyrrolo[3,2-c]pyridine-2-carboxamideN-{[4-(6-methoxypyridine-2-sulfonyl)phenyl]methyl}imidazo[1,2-a]pyrimidine-6-carboxamideN-({4-[2-(trifluoromethyl)imidazo[1,2-a]pyridine-6-sulfonyl]phenyl}methyl)furo[2,3-c]pyridine-2-carboxamideN-({4-[1-(4-fluorophenyl)-1H-pyrazole-4-sulfonyl]phenyl}methyl)-1H-pyrrolo[3,2-c]pyridine-2-carboxamideN-{[4-(1-methyl-1H-pyrazole-4-sulfonyl)phenyl]methyl}-1H-pyrrolo[3,2-c]pyridine-2-carboxamideN-{[4-(1-methyl-1H-indazole-5-sulfonyl)phenyl]methyl}furo[2,3-c]pyridine-2-carboxamideN-{[4-(1-methyl-1H-indazole-7-sulfonyl)phenyl]methyl}imidazo[1,2-a]pyrimidine-6-carboxamideN-({4-[5-(trifluoromethyl)pyridine-3-sulfonyl]phenyl}methyl)imidazo[1,2-a]pyridine-6-carboxamideN-{[4-(5-methoxypyridine-2-sulfonyl)phenyl]methyl}furo[2,3-c]pyridine-2-carboxamideN-({4-[1-(3-chlorophenyl)-1H-pyrazole-4-sulfonyl]phenylmethyl)-1H-pyrrolo[3,2-c]pyridine-2-carboxamideN-{[4-(6-methylpyridine-3-sulfonyl)phenyl]methyl}imidazo[1,2-a]pyrimidine-6-carboxamideN-({4-[6-(dimethylamino)pyridine-3-sulfonyl]phenyl}methyl)furo[2,3-c]pyridine-2-carboxamideN-({4-[1-(propan-2-yl)-1H-pyrazole-4-sulfonyl]phenyl}methyl)imidazo[1,2-a]pyridine-6-carboxamideN-{[4-(isoquinoline-4-sulfonyl)phenyl]methyl}furo[2,3-c]pyridine-2-carboxamideN-({4-[2-(pyrrolidin-1-yl)-1,3-thiazole-5-sulfonyl]phenyl}methyl)imidazo[1,2-a]pyrimidine-6-carboxamideN-[(4-{5H,6H,7H,8H,9H-imidazo[azepine-3-sulfonyl}phenyl)methyl]furo[2,3-c]pyridine-2-carboxamideN-({4-[5-(pyrrolidin-1-yl)pyridine-3-sulfonyl]phenyl}methyl)-1,3-benzothiazole-6-carboxamideN-{[4-(5-fluoro-6-methylpyridine-2-sulfonyl)phenyl]methyl}furo[2,3-c]pyridine-2-carboxamideN-({4-[4-(trifluoromethyl)pyridine-2-sulfonyl]phenyl}methyl)imidazo[1,2-a]pyrimidine-6-carboxamideN-{[4-(dimethyl-1,3-thiazole-5-sulfonyl)phenyl]methyl}thieno[2,3-c]pyridine-2-carboxamideN-[(4-{6-chloroimidazo[1,2-a]pyridine-3-sulfonyl}phenyl)methyl]-1H-pyrrolo[3,2-c]pyridine-2-carboxamideN-({4-[6-(morpholin-4-yl)pyridine-3-sulfonyl]phenyl}methyl)thieno[2,3-c]pyridine-2-carboxamideN-{[4-(5-methoxypyridine-2-sulfonyl)phenyl]methyl}thieno[2,3-c]pyridine-2-carboxamideN-{[4-(isoquinoline-4-sulfonyl)phenyl]methyl-1H-pyrazolo[3,4-b]pyridine-5-carboxamideN-{[4-(4-methylpyridine-3-sulfonyl)phenyl]methyl}thieno[2,3-c]pyridine-2-carboxamideN-{[4-(1-methyl-1H-indazole-4-sulfonyl)phenyl]methyl}thieno[2,3-c]pyridine-2-carboxamideN-({4-[6-(dimethylamino)pyridine-3-sulfonyl]phenyl}methyl)-1H-pyrazolo[3,4-b]pyridine-5-carboxamideN-({4-[1-(3-chlorophenyl)-1H-pyrazole-4-sulfonyl]phenyl}methyl)imidazo[1,2-a]pyrimidine-6-carboxamideN-[(4-{2-[ethyl(methyl)amino]-1,3-thiazole-5-sulfonyl}phenyl)methyl]imidazo[1,2-a]pyridine-6-carboxamideN-({4-[5-(trifluoromethyl)pyridine-2-sulfonyl]phenyl}methyl)imidazo[1,2-a]pyridine-6-carboxamideN-{[4-(5-fluoropyridine-3-sulfonyl)phenyl]methyl}thieno[2,3-c]pyridine-2-carboxamideN-({4-[5-(trifluoromethyl)pyridine-2-sulfonyl]phenyl}methyl)furo[2,3-c]pyridine-2-carboxamideN-[(4-{2-[ethyl(methyl)amino]-1,3-thiazole-5-sulfonyl}phenyl)methyl]imidazo[1,2-a]pyrimidine-6-carboxamideN-{[4-(5-methylpyridine-3-sulfonyl)phenyl]methyl}thieno[2,3-c]pyridine-2-carboxamideN-[(4-{6-chloroimidazo[1,2-a]pyridine-3-sulfonyl}phenyl)methyl]furo[2,3-c]pyridine-2-carboxamideN-{[4-(2-methyl-2H-indazole-6-sulfonyl)phenyl]methyl}-1H-pyrrolo[3,2-c]pyridine-2-carboxamideN-{[4-(5-methylpyridine-3-sulfonyl)phenyl]methyl}imidazo[1,2-a]pyridine-6-carboxamide5-hydroxy-N-{[4-(1-methyl-1H-indazole-4-sulfonyl)phenyl]methyl}-1H-indole-2-carboxamideN-{[4-(2,6-dimethoxypyridine-3-sulfonyl)phenyl]methyl}furo[2,3-c]pyridine-2-carboxamideN-({4-[1-methyl-5-(trifluoromethyl)-1H-pyrazole-4-sulfonyl]phenyl}methyl)-1H-pyrazolo[3,4-b]pyridine-5-carboxamideN-({4-[2-(dimethylamino)pyrimidine-5-sulfonyl]phenyl}methyl)thieno[2,3-c]pyridine-2-carboxamideN-{[4-(6-methylpyridine-3-sulfonyl)phenyl]methyl}thieno[2,3-c]pyridine-2-carboxamideN-[(4-{6-chloroimidazo[1,2-a]pyridine-3-sulfonyl}phenyl)methyl]thieno[2,3-c]pyridine-2-carboxamideN-({4-[1-(4-fluorophenyl)-1H-pyrazole-4-sulfonyl]phenyl}methyl)furo[2,3-c]pyridine-2-carboxamideN-({4-[6-(3,4-difluorophenyl)pyridine-2-sulfonyl]phenyl}methyl)imidazo[1,2-a]pyridine-6-carboxamideN-({4-[6-(morpholin-4-yl)pyridine-3-sulfonyl]phenyl}methyl)-1H-pyrrolo[3,2-c]pyridine-2-carboxamideN-{[4-(1,5-dimethyl-1H-imidazole-2-sulfonyl)phenyl]methyl}imidazo[1,2-a]pyrimidine-6-carboxamideN-{[4-(1-methyl-1H-indazole-7-sulfonyl)phenyl]methyl}thieno[2,3-c]pyridine-2-carboxamideN-{[4-(2-methyl-2H-indazole-6-sulfonyl)phenyl]methyl}imidazo[1,2-a]pyrimidine-6-carboxamideN-{[4-(1,5-dimethyl-1H-imidazole-2-sulfonyl)phenyl]methyl}furo[2,3-c]pyridine-2-carboxamideN-{[4-(isoquinoline-4-sulfonyl)phenyl]methyl}-1H-pyrrolo[3,2-c]pyridine-2-carboxamideN-({4-[6-(dimethylamino)pyridine-3-sulfonyl]phenyl}methyl)imidazo[1,2-a]pyridine-6-carboxamideN-({4-[6-(3,4-difluorophenyl)pyridine-2-sulfonyl]phenyl}methyl)-1H-pyrrolo[3,2-c]pyridine-2-carboxamideN-({4-(2-(trifluoromethyl)imidazo[1,2-a]pyridine-6-sulfonyl]phenyl}methyl)imidazo[1,2-a]pyridine-6-carboxamideN-{[4-(5-chloropyridine-3-sulfonyl)phenyl]methyl}imidazo[1,2-a]pyridine-6-carboxamideN-{[4-(4-methylpyridine-3-sulfonyl)phenyl]methyl}-1H-pyrazolo[3,4-b]pyridine-5-carboxamideN-{[4-(pyridine-3-sulfonyl)phenyl]methyl}furo[2,3-c]pyridine-2-carboxamideN-{[4-(1-methyl-1H-indazole-4-sulfonyl)phenyl]methyl}furo[2,3-c]pyridine-2-carboxamideN-({4-[6-(dimethylamino)pyridine-3-sulfonyl]phenyl}methyl)thieno[2,3-c]pyridine-2-carboxamideN-{[4-(1,4-dimethyl-1H-imidazole-2-sulfonyl)phenyl]methyl}furo[2,3-c]pyridine-2-carboxamideN-{[4-(5-methylpyridine-3-sulfonyl)phenyl]methyl}imidazo[1,2-a]pyrimidine-6-carboxamideN-({4-[4-(trifluoromethyl)pyridine-2-sulfonyl]phenyl}methyl)-1H-pyrazolo[3,4-b]pyridine-5-carboxamideN-[(4-{5H,6H,7H,8H,9H-imidazo[1,2-a]azepine-3-sulfonyl}phenyl)methyl]-1H-pyrazolo[3,4-b]pyridine-5-carboxamideN-{[4-(2-methyl-2H-indazole-6-sulfonyl)phenyl]methyl}imidazo[1,2-a]pyridine-6-carboxamideN-{[4-(5-fluoropyridine-3-sulfonyl)phenyl]methyl}imidazo[1,2-a]pyrimidine-6-carboxamideN-{[4-(5-chloropyridine-3-sulfonyl)phenyl]methyl}-1H-pyrazolo[3,4-b]pyridine-5-carboxamideN-{[4-(1-methyl-1H-indazole-6-sulfonyl)phenyl]methyl}furo[2,3-c]pyridine-2-carboxamideN-{[4-(1H-indole-7-sulfonyl)phenyl]methyl}-1H-pyrazolo[3,4-b]pyridine-5-carboxamideN-{[4-(5-fluoropyridine-3-sulfonyl)phenyl]methyl}-1H-pyrrolo[3,2-c]pyridine-2-carboxamideN-({4-[2-(dimethylamino)pyrimidine-5-sulfonyl]phenyl}methyl)furo[2,3-c]pyridine-2-carboxamideN-({4-[5-(dimethylamino)pyrazine-2-sulfonyl]phenyl}methyl)imidazo[1,2-a]pyridine-6-carboxamideN-{[4-(5-methoxypyridine-3-sulfonyl)phenyl]methylimidazo[1,2-a]pyrimidine-6-carboxamideN-({4-[2-(trifluoromethyl)pyridine-3-sulfonyl]phenyl}methyl)furo[2,3-c]pyridine-2-carboxamideN-{[4-(pyridine-3-sulfonyl)phenyl]methyl}-1H-pyrrolo[3,2-c]pyridine-2-carboxamideN-{[4-(6-methylpyridine-3-sulfonyl)phenyl]methyl}imidazo[1,2-a]pyridine-6-carboxamideN-{[4-(1,5-dimethyl-1H-imidazole-2-sulfonyl)phenyl]methyl}imidazo[1,2-a]pyridine-6-carboxamideN-{[4-(1-methyl-1H-indazole-6-sulfonyl)phenyl]methyl}-1H-pyrrolo[3,2-c]pyridine-2-carboxamideN-({4-[3-chloro-2-(morpholin-4-yl)pyridine-4-sulfonyl]phenylmethyl)thieno[2,3-c]pyridine-2-carboxamideN-{[4-(1,3-thiazole-2-sulfonyl)phenyl]methyl}furo[2,3-c]pyridine-2-carboxamideN-({4-[5-(trifluoromethyl)pyridine-2-sulfonyl]phenylmethyl)-1H-pyrazolo[3,4-b]pyridine-5-carboxamideN-{[4-(2-methylpyridine-3-sulfonyl)phenyl]methyl}-1H-pyrazolo[3,4-b]pyridine-5-carboxamideN-{[4-(6-methylpyridine-2-sulfonyl)phenyl]methyl}furo[2,3-c]pyridine-2-carboxamideN-{[4-(1-methyl-1H-indazole-5-sulfonyl)phenyl]methyl}thieno[2,3-c]pyridine-2-carboxamideN-({4-[4-(trifluoromethyl)pyridine-2-sulfonyl]phenyl}methyl)imidazo[1,2-a]pyridine-6-carboxamideN-({4-[4-(trifluoromethyl)pyridine-2-sulfonyl]phenyl}methyl)furo[2,3-c]pyridine-2-carboxamideN-{[4-(4-methylpyridine-3-sulfonyl)phenyl]methyl}imidazo[1,2-a]pyrimidine-6-carboxamideN-[4-(1,4-dimethyl-1H-imidazole-2-sulfonyl)phenyl]methyl}imidazo[1,2-a]pyridine-6-carboxamideN-({4-[2-(dimethylamino)pyrimidine-5-sulfonyl]phenyl}methyl)imidazo[1,2-a]pyridine-6-carboxamideN-{[4-(1-methyl-1H-pyrazole-4-sulfonyl)phenyl]methyl}imidazo[1,2-a]pyrimidine-6-carboxamideN-{[4-(5-chloro-3-methylpyridine-2-sulfonyl)phenyl]methyl}imidazo[1,2-a]pyridine-6-carboxamideN-({4-[2-(3-fluorophenyl)-1,3-thiazole-4-sulfonyl]phenyl}methyl)-1H-pyrazolo[3,4-b]pyridine-5-carboxamideN-{[4-(5-methoxypyridine-3-sulfonyl)phenyl]methyl}thieno[2,3-c]pyridine-2-carboxamideN-{[4-(2-methyl-2H-indazole-6-sulfonyl)phenyl]methyl}furo[2,3-c]pyridine-2-carboxamideN-{[4-(1-benzothiophene-7-sulfonyl)phenyl]methyl}-1H-pyrazolo[3,4-b]pyridine-5-carboxamideN-({4-[6-(morpholin-4-yl)pyridine-3-sulfonyl]phenyl}methyl)imidazo[1,2-a]pyridine-6-carboxamideN-({4[5-(pyrrolidin-1-yl)pyridine-3-sulfonyl]phenyl}methyl)-1H-pyrazolo[3,4-b]pyridine-5-carboxamideN-[(4-{2-[ethyl(methyl)amino]-1,3-thiazole-5-sulfonyl}phenyl)methyl]furo[2,3-c]pyridine-2-carboxamideN-({4-[1-(3-chlorophenyl)-1H-pyrazole-4-sulfonyl]phenyl}methyl)furo[2,3-c]pyridine-2-carboxamideN-[(4-{5H,6H,7H,8H,9H-imidazo[1,2-a]azepine-3-sulfonyl}phenyl)methyl]imidazo[1,2-a]pyrimidine-6-carboxamideN-{[4-(2-methyl-1,3-thiazole-4-sulfonyl)phenyl]methyl-1H-pyrazolo[3,4-b]pyridine-5-carboxamideN-({4-[6-(4-methylpiperazin-1-yl)pyridine-3-sulfonyl]phenyl}methyl)-1H-pyrrolo[3,2-c]pyridine-2-carboxamideN-{[4-(2-methyl-1,3-thiazole-4-sulfonyl)phenyl]methyl}furo[2,3-c]pyridine-2-carboxamideN-{[4-(1-methyl-1H-indazole-4-sulfonyl)phenyl]methyl}-1H-pyrazolo[3,4-b]pyridine-5-carboxamideN-{[4-(1-propyl-1H-pyrazole-4-sulfonyl)phenyl]methyl}imidazo[1,2-a]pyridine-6-carboxamideN-{[4-(5-fluoropyridine-3-sulfonyl)phenyl]methyl}-1H-pyrazolo[3,4-b]pyridine-5-carboxamideN-[(4-{5H,6H,7H,8H,9H-imidazo[1,2-a]azepine-3-sulfonyl}phenyl)methyl]thieno[2,3-c]pyridine-2-carboxamideN-{[4-(1-methyl-1H-indole-2-sulfonyl)phenyl]methyl}thieno[2,3-c]pyridine-2-carboxamideN-[(4-{6-chloroimidazo[1,2-a]pyridine-3-sulfonyl}phenyl)methyl]-1H-pyrazolo[3,4-b]pyridine-5-carboxamideN-{[4-(5-chloro-3-methylpyridine-2-sulfonyl)phenyl]methyl}-1H-pyrazolo[3,4-b]pyridine-5-carboxamideN-{[4-(1-propyl-1H-pyrazole-4-sulfonyl)phenyl]methyl}thieno[2,3-c]pyridine-2-carboxamideN-{[4-(4-methylpyridine-3-sulfonyl)phenyl]methyl}imidazo[1,2-a]pyridine-6-carboxamideN-{[4-(5-methoxypyridine-3-sulfonyl)phenyl]methyl}imidazo[1,2-a]pyridine-6-carboxamideN-({4-[1-methyl-3-(trifluoromethyl)-1H-pyrazole-4-sulfonyl]phenyl}methyl)imidazo[1,2-a]pyridine-6-carboxamideN-{[4-(5-methylthiophene-2-sulfonyl)phenyl]methyl}thieno[2,3-c]pyridine-2-carboxamideN-({4-[6-(morpholin-4-yl)pyridine-3-sulfonyl]phenyl}methyl)furo[2,3-c]pyridine-2-carboxamideN-{[4-(6-methylpyrazine-2-sulfonyl)phenyl]methyl}furo[2,3-c]pyridine-2-carboxamideN-{[4-(1-methyl-1H-indazole-4-sulfonyl)phenyl]methyl}-1,3-benzothiazole-6-carboxamideN-{[4-(2,6-dimethoxypyridine-3-sulfonyl)phenyl]methyl}imidazo[1,2-a]pyridine-6-carboxamideN-[(4-{6-chloroimidazo[1,2-a]pyridine-3-sulfonyl}phenyl)methyl]imidazo[1,2-a]pyridine-6-carboxamideN-{[4-(2-methyl-1,3-thiazole-4-sulfonyl)phenyl]methyl}imidazo[1,2-a]pyrimidine-6-carboxamideN-{[4-(1-propyl-1H-pyrazole-4-sulfonyl)phenyl]methyl}furo[2,3-c]pyridine-2-carboxamideN-{[4-(dimethyl-1,3-thiazole-5-sulfonyl)phenyl]methyl}imidazo[1,2-a]pyridine-6-carboxamideN-{[4-(5-methoxypyridine-3-sulfonyl)phenyl]methyl}-1H-pyrazolo[3,4-b]pyridine-5-carboxamideN-{[4-(5-fluoropyridine-3-sulfonyl)phenyl]methyl}imidazo[1,2-a]pyridine-6-carboxamideN-[(4-{2-[ethyl(methyl)amino]-1,3-thiazole-5-sulfonyl}phenyl)methyl]-1H-pyrazolo[3,4-b]pyridine-5-carboxamideN-{[4-(2-methyl-2H-indazole-5-sulfonyl)phenyl]methyl}imidazo[1,2-a]pyridine-6-carboxamideN-{[4-(2-methyl-2H-indazole-5-sulfonyl)phenyl]methyl}thieno[2,3-c]pyridine-2-carboxamideN-({4-[2-(3-fluorophenyl)-1,3-thiazole-4-sulfonyl]phenyl}methyl)thieno[2,3-c]pyridine-2-carboxamideN-{[4-(1-benzothiophene-7-sulfonyl)phenyl]methyl}thieno[2,3-c]pyridine-2-carboxamideN-{[4-(1-methyl-1H-indazole-4-sulfonyl)phenyl]methyl}imidazo[1,2-a]pyridine-6-carboxamideN-{[4-(4-methylthiophene-2-sulfonyl)phenyl]methyl}imidazo[1,2-a]pyridine-6-carboxamideN-({4-[2-(3-fluorophenyl)-1,3-thiazole-4-sulfonyl]phenyl}methyl)imidazo[1,2-a]pyridine-6-carboxamideN-{[4-(2,6-dimethoxypyridine-3-sulfonyl)phenyl]methyl}-1H-pyrazolo[3,4-b]pyridine-5-carboxamideN-{[4-(pyridine-3-sulfonyl)phenyl]methylimidazo[1,2-a]pyrimidine-6-carboxamideN-({4-[2-(pyrrolidin-1-yl)-1,3-thiazole-5-sulfonyl]phenyl}methyl)thieno[2,3-c]pyridine-2-carboxamideN-{[4-(5-methoxypyridine-2-sulfonyl)phenyl]methyl}imidazo[1,2-a]pyridine-6-carboxamideN-{[4-(1-methyl-1H-indazole-5-sulfonyl)phenyl]methyl}imidazo[1,2-a]pyrimidine-6-carboxamideN-{[4-(6-methylpyridine-3-sulfonyl)phenyl]methyl}-1H-pyrrolo[3,2-c]pyridine-2-carboxamideN-({4-[2-(pyrrolidin-1-yl)-1,3-thiazole-5-sulfonyl]phenyl}methyl)-1H-pyrazolo[3,4-b]pyridine-5-carboxamideN-({4-[6-(morpholin-4-yl)pyridine-3-sulfonyl]phenyl}methyl)imidazo[1,2-a]pyrimidine-6-carboxamideN-({4-[1-(3-chlorophenyl)-1H-pyrazole-4-sulfonyl]phenyl}methyl)thieno[2,3-c]pyridine-2-carboxamideN-{[4-(pyridine-2-sulfonyl)phenyl]methylfuro[2,3-c]pyridine-2-carboxamideN-{[4-(4-methylpyridine-3-sulfonyl)phenyl]methyl}furo[2,3-c]pyridine-2-carboxamideN-({4-[2-(morpholin-4-yl)pyridine-3-sulfonyl]phenyl}methyl)furo[2,3-c]pyridine-2-carboxamideN-{[4-(1,4-dimethyl-1H-imidazole-2-sulfonyl)phenyl]methyl}imidazo[1,2-a]pyrimidine-6-carboxamideN-{[4-(1-methyl-1H-indole-2-sulfonyl)phenyl]methyl-1H-pyrazolo[3,4-b]pyridine-5-carboxamideN-({4-[2-(pyrrolidin-1-yl)-1,3-thiazole-5-sulfonyl]phenyl}methyl)imidazo[1,2-a]pyridine-6-carboxamideN-{[4-(dimethyl-1,3-thiazole-5-sulfonyl)phenyl]methyl}furo[2,3-c]pyridine-2-carboxamideN-{[4-(6-methoxypyridine-2-sulfonyl)phenyl]methyl}imidazo[1,2-a]pyridine-6-carboxamideN-({4-[6-(trifluoromethyl)pyridine-2-sulfonyl]phenyl}methyl)imidazo[1,2-a]pyridine-6-carboxamideN-{[4-(1-methyl-1H-pyrazole-4-sulfonyl)phenyl]methyl}furo[2,3-c]pyridine-2-carboxamideN-{[4-(4-methylpyridine-2-sulfonyl)phenyl]methyl}furo[2,3-c]pyridine-2-carboxamideN-{[4-(furan-2-sulfonyl)phenyl]methyl}imidazo[1,2-a]pyridine-6-carboxamideN-{[4-(1-methyl-1H-indazole-4-sulfonyl)phenyl]methyl}-1H-pyrrolo[3,2-c]pyridine-2-carboxamideN-{[4-(1-methyl-1H-indazole-6-sulfonyl)phenyl]methyl}-1H-pyrazolo[3,4-b]pyridine-5-carboxamideN-({4-[6-(3,4-difluorophenyl)pyridine-2-sulfonyl]phenyl}methyl)furo[2,3-c]pyridine-2-carboxamideN-{[4-(1-methyl-1H-indazole-7-sulfonyl)phenyl]methyl}-1H-pyrrolo[3,2-c]pyridine-2-carboxamideN-{[4-(1-methyl-1H-indazole-5-sulfonyl)phenyl]methyl}-1H-pyrrolo[3,2-c]pyridine-2-carboxamideN-{[4-(1-methyl-1H-pyrazole-4-sulfonyl)phenyl]methyl}-1H-pyrazolo[3,4-b]pyridine-5-carboxamideN-{[4-(5-methylthiophene-2-sulfonyl)phenyl]methyl}-1H-pyrazolo[3,4-b]pyridine-5-carboxamideN-{[4-(1-methyl-1H-indazole-5-sulfonyl)phenyl]methyl}-1H-pyrazolo[3,4-b]pyridine-5-carboxamideN-{[4-(1-methyl-1H-indazole-7-sulfonyl)phenyl]methyl}-1H-pyrazolo[3,4-b]pyridine-5-carboxamideor a pharmaceutically acceptable salt thereof.
 34. A compound of formulaIIB :

or pharmaceutically acceptable salt thereof wherein: R is 9 to 10membered bicyclic heteroaryl groups containing 1, 2, 3, or 4 heteroatomsindependently selected from N, S, and O, wherein said heteroaryl may besubstituted by one or more substituents selected from the groupconsisting of amino, oxo, and halo; and wherein said heteroaryl cancomprise one or more N-oxide(s) formed with a N atom member of saidheteroaryl; R¹ is heteroaryl, wherein: said heteroaryl is unsubstitutedor substituted with 1, 2, 3, 4, or 5 substituents which can be the sameor different and are independently selected from the group consistingof: halo, hydroxy, hydroxyalkyl, cyano, alkyl, alkynyl, alkynylalkoxy,alkoxyalkyl, alkoxy, haloalkyl, haloalkoxy, —C(O)NH(alkyl),—C(O)NH(cycloalkyl), —C(O)N(alkyl)₂, arylalkoxy-, aryloxy-, cycloalkyl,heterocycloalkyl, aryl, (heterocycloalkyl)alkyl-,(heterocycloalkyl)alkoxy-, —C(O)heterocycloalkyl, heteroaryl,(heteroaryl)alkyl-, —S(O)₂-alkyl, —S-alkyl, —C(O)alkyl, —S(O)₂NH₂,—S(O₂)NH(alkyl), —S(O)₂N(alkyl)₂, and —N(H)(SO₂)(alkyl), wherein each ofsaid cycloalkyl, heterocycloalkyl, aryl, or heteroaryl may besubstituted by one or more halo, cyano, alkyl, and alkoxy; and saidheteroaryl may optionally additionally be fused with independentlyselected heterocycloalkyl or cycloalkyl to form a bicyclic or tricyclicgroup that may be substituted by one or more halo, cyano, alkyl, andalkoxy; R² and R³ can be independently selected from the groupconsisting of H and deuterium; R⁵ is H, alkyl, or arylalkyl; R^(a) andR^(b) are independently selected from the group consisting of H, alkyl,alkoxy, alkoxyalkyl, and haloalkyl; m is 0, 1, 2, 3, 4, 5, or 6; and zis 0, 1, or
 2. 35. The compound of claim 34, wherein R¹ is heteroaryl,wherein said heteroaryl is unsubstituted or substituted with 1, 2, 3, 4,or 5 substituents which can be the same or different and areindependently selected from the group consisting of: halo, haloalkyl,and haloalkoxy.
 36. The compound of claim 35, wherein haloalkyl is—CH_(z)F_(3−z) or —CH₂CH_(z)F_(3−z), and z is 0, 1, or
 2. 37. Thecompound of claim 35, wherein haloalkoxy is —OCH_(z)F_(3−z), and z is 0,1, or
 2. 36. The compound of claim 35, wherein halo is F.
 37. Apharmaceutical composition comprising a compound of claim 21 and apharmaceutically acceptable carrier.
 38. A pharmaceutical compositioncomprising a compound of claim 34 and a pharmaceutically acceptablecarrier.